Protein Data Bank (PDB)
English
United States, San Diego
PDB
数据描述
The RCSB Protein Data Bank (RCSB PDB) dataset provides open access to structural biology data for exploration, visualization, and analysis. It contains experimentally determined 3D macromolecular structures from the worldwide PDB archive, integrative 3D structures modeling complex assemblies, and computed structure models (CSMs) aggregated from AlphaFold DB and ModelArchive. The collection supports research and education by enabling users to search, browse annotations, and analyze protein, nucleic-acid, and complex structures, including associated model metadata and validation-related information accessible via APIs. As of June 2025, it spans roughly 238,000 experimental PDB structures plus over 1 million computed models.
www.rcsb.org
IP: 132.249.210.225
加载中...
相关论文
744Antibody-dependent enhancement (ADE) of SARS-CoV-2 pseudoviral infection requires FcγRIIB and virus-antibody complex with bivalent interaction
Wang Shuang•Wang Junchao•Yu Xiaojuan•Jiang Wen•Chen Shuo等 23 人
Communications Biology
2022
•2022/3/24
•Vol.5 No.1 p.1-9
Understanding the underlying molecular mechanisms behind ADE of SARS-CoV-2 is critical for development of safe and effective therapies. Here, we report that two neutralizing mAbs, MW01 and MW05, could enhance the infection of SARS-CoV-2 pseudovirus on FcγRIIB-expressing B cells. X-ray crystal struct...
Infectious diseasesSARS-CoV-2
10.1038/S42003-022-03207-0
ISSN:2399-3642
Systematic proteome-wide Mendelian randomization to prioritize causal plasma proteins for skin cancers
Masahiro Yoshikawa•Tomohiro Nakayama•Kensuke Asaba
Communications Biology
2024
•2024/12/19
•Vol.7 No.1 p.1-11
Skin cancer is one of the most common cancers worldwide. Some risk factors including sun exposure and MC1R variants are recognized; however, the identification of additional genetic factors is essential for the development of novel therapeutic strategies. Here, we conducted a proteome-wide Mendelian...
Data integrationSkin cancer
10.1038/S42003-024-07403-Y
ISSN:2399-3642
Mapping protein binding sites by photoreactive fragment pharmacophores
Péter Ábrányi-Balogh•Dávid Bajusz•Zoltán Orgován•Aaron B. Keeley•László Petri等 24 人
Communications Chemistry
2024
•2024/7/31
•Vol.7 No.1 p.1-13
Fragment screening is a popular strategy of generating viable chemical starting points especially for challenging targets. Although fragments provide a better coverage of chemical space and they have typically higher chance of binding, their weak affinity necessitates highly sensitive biophysical as...
Chemical librariesChemical toolsDrug discovery and developmentScreening
10.1038/S42004-024-01252-W
ISSN:2399-3669
Deep phylogeny of cancer drivers and compensatory mutations
Nash D. Rochman•Yuri I. Wolf•Eugene V. Koonin
Communications Biology
2020
•2020/10/2
•Vol.3 No.1 p.1-11
Driver mutations (DM) are the genetic impetus for most cancers. The DM are assumed to be deleterious in species evolution, being eliminated by purifying selection unless compensated by other mutations. We present deep phylogenies for 84 cancer driver genes and investigate the prevalence of 434 DM ac...
Cancer genomicsCoevolution
10.1038/S42003-020-01276-7
ISSN:2399-3642
Epigenetic mechanisms to propagate histone acetylation by p300/CBP
Masaki Kikuchi•Satoshi Morita•Masatoshi Wakamori•Shin Sato•Tomomi Uchikubo-Kamo等 9 人
Nature Communications
2023
•2023/7/17
•Vol.14 No.1 p.1-16
Histone acetylation is important for the activation of gene transcription but little is known about its direct read/write mechanisms. Here, we report cryogenic electron microscopy structures in which a p300/CREB-binding protein (CBP) multidomain monomer recognizes histone H4 N-terminal tail (NT) ace...
Chemical modificationCryoelectron microscopy
10.1038/S41467-023-39735-4
ISSN:2041-1723
Molecular basis for the diversification of lincosamide biosynthesis by pyridoxal phosphate-dependent enzymes
Takahiro Mori•Yoshitaka Moriwaki•Kosuke Sakurada•Shuang Lyu•Stanislav Kadlcik等 11 人
Nature Chemistry
2024
•2024/12/6
•00 p.1-9
The biosynthesis of the lincosamide antibiotics lincomycin A and celesticetin involves the pyridoxal-5′-phosphate (PLP)-dependent enzymes LmbF and CcbF, which are responsible for bifurcation of the biosynthetic pathways. Despite recognizing the same S-glycosyl-l-cysteine structure of the substrates,...
Enzyme mechanismsX-ray crystallography
10.1038/S41557-024-01687-7
ISSN:1755-4330
Structure of bifunctional variediene synthase yields unique insight on biosynthetic diterpene assembly and cyclization
Eliott S. Wenger•David W. Christianson
Nature Communications
2025
•2025/6/2
•Vol.16 No.1 p.1-12
An unusual family of bifunctional terpene synthases has been identified in which a prenyltransferase assembles 5-carbon precursors to form C20 geranylgeranyl diphosphate (GGPP), which is then converted into a polycyclic product by a cyclase. Here, we report the cryo-EM structure of a massive, 495-kD...
BiocatalysisCryoelectron microscopyEnzymesNatural product synthesis
10.1038/S41467-025-60537-3
ISSN:2041-1723
Precisely patterned nanofibres made from extendable protein multiplexes
Neville P. Bethel•Andrew J. Borst•Fabio Parmeggiani•Matthew J. Bick•TJ Brunette等 15 人
Nature Chemistry
2023
•2023/9/4
•00 p.1-8
Molecular systems with coincident cyclic and superhelical symmetry axes have considerable advantages for materials design as they can be readily lengthened or shortened by changing the length of the constituent monomers. Among proteins, alpha-helical coiled coils have such symmetric, extendable arch...
Nanoscale materialsProtein designProtein folding
10.1038/S41557-023-01314-X
ISSN:1755-4330
Accelerating the discovery of alkyl halide-derived natural products using halide depletion
Nathaniel R. Glasser•Dongtao Cui•Douglas D. Risser•C. Denise Okafor•Emily P. Balskus
Nature Chemistry
2024
•2024/1/12
•00 p.1-10
Even in the genomic era, microbial natural product discovery workflows can be laborious and limited in their ability to target molecules with specific structural features. Here we leverage an understanding of biosynthesis to develop a workflow that targets the discovery of alkyl halide-derived natur...
MetabolomicsNatural products
10.1038/S41557-023-01390-Z
ISSN:1755-4330
A viral ADP-ribosyltransferase attaches RNA chains to host proteins
Maik Wolfram-Schauerte•Nadiia Pozhydaieva•Julia Grawenhoff•Luisa M. Welp•Ivan Silbern等 11 人
Nature
2023
•2023/8/16
•00 p.1-9
The mechanisms by which viruses hijack the genetic machinery of the cells they infect are of current interest. When bacteriophage T4 infects Escherichia coli, it uses three different adenosine diphosphate (ADP)-ribosyltransferases (ARTs) to reprogram the transcriptional and translational apparatus o...
Phage biologyPost-translational modificationsProteomicsRNA
10.1038/S41586-023-06429-2
ISSN:0028-0836
A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants
Yang Zhenlin•Wang Yulu•Jin Yujia•Zhu Yuanfei•Wu Yanling等 26 人
Signal Transduction And Targeted Therapy
2021
•2021/11/3
•Vol.6 No.1 p.1-8
The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants....
Infectious diseasesStructural biology
10.1038/S41392-021-00810-1
ISSN:2059-3635
MHC class II functions as a host-specific entry receptor for representative human and swine H3N2 influenza A viruses
Matias Cardenas•Sasha Compton•C. Joaquin Caceres•Adolfo García-Sastre•Daniel R. Perez等 6 人
Nature Communications
2026
•2026/2/10
•Vol.17 No.1 p.25600
Influenza A viruses (FLUAV) utilize sialic acid to enter host cells via the envelope’s hemagglutinin (HA), and its affinity for host-specific sialic acid linkage configuration is a major host range determinant. However, some FLUAV subtypes (H17, H18, H19) use the major histocompatibility complex cla...
Influenza virusVirus–host interactions
10.1038/S41467-026-69267-6
ISSN:2041-1723
Mechanistic basis for improved activity of Engineered AsCas12a
Linnea Jansson-Fritzberg•Bryant Chica•Chrysa Latrick•Andrea Olland•Alexey Dementiev等 9 人
Communications Biology
2026
•2026/3/10
0CRISPR-associated proteins (Cas) are central to gene editing, forming nuclease complexes with guide RNA to enable precise genome modification. Among numerous Cas variants, Cas9 and Cas12a are the most extensively studied. While much is known about the genomic substrates for these enzymes, less is kn...
CRISPR-Cas9 genome editingEnzyme mechanismsX-ray crystallography
10.1038/S42003-026-09799-1
ISSN:2399-3642
A unified cross-attention model for predicting antigen binding specificity to both HLA and TCR molecules
Chenpeng Yu•Xing Fang•Shiye Tian•Hui Liu
Nature Machine Intelligence
2025
•2025/1/28
•Vol.7 No.2 p.278-292
The immune checkpoint inhibitors have demonstrated promising clinical efficacy across various tumour types, yet the percentage of patients who benefit from them remains low. The bindings between tumour antigens and human leukocyte antigen class I/T cell receptor molecules determine the antigen prese...
Computational modelsMachine learningSARS-CoV-2
10.1038/S42256-024-00973-W
ISSN:2522-5839
A graphic and command line protocol for quick and accurate comparisons of protein and nucleic acid structures with US-align
Chengxin Zhang•Lydia Freddolino•Yang Zhang
Nature Protocols
2025
•2025/7/2
•00 p.1-25
With the success of structural biology and the advancements in deep-learning-based structure predictions, rapid and accurate structural comparisons among macromolecular structures have become increasingly important in structural bioinformatics. US-align is a highly efficient, versatile, open-source ...
BioinformaticsComputational platforms and environmentsProtein function predictionsProtein structure predictions
10.1038/S41596-025-01189-X
ISSN:1754-2189
Structural elucidation of recombinant Trichomonas vaginalis 20S proteasome bound to covalent inhibitors
Jan Silhan•Pavla Fajtova•Jitka Bartosova•Brianna M. Hurysz•Jehad Almaliti等 10 人
Nature Communications
2024
•2024/10/4
•Vol.15 No.1 p.1-12
The proteasome is a proteolytic enzyme complex essential for protein homeostasis in mammalian cells and protozoan parasites like Trichomonas vaginalis (Tv), the cause of the most common, non-viral sexually transmitted disease. Tv and other protozoan 20S proteasomes have been validated as druggable t...
Cryoelectron microscopyParasite biologyProteasome
10.1038/S41467-024-53022-W
ISSN:2041-1723
Structural basis for the assembly and quinone transport mechanisms of the dimeric photosynthetic RC–LH1 supercomplex
Cao Peng•Bracun Laura•Yamagata Atsushi•Christianson Bern M.•Negami Tatsuki等 11 人
Nature Communications
2022
•2022/4/13
•Vol.13 No.1 p.1-12
The reaction center (RC) and light-harvesting complex 1 (LH1) form a RC–LH1 core supercomplex that is vital for the primary reactions of photosynthesis in purple phototrophic bacteria. Some species possess the dimeric RC–LH1 complex with a transmembrane polypeptide PufX, representing the largest pho...
BacteriaCryoelectron microscopyMembrane proteinsPhotosynthesis
10.1038/S41467-022-29563-3
ISSN:2041-1723
Structural insight into the human SID1 transmembrane family member 2 reveals its lipid hydrolytic activity
Dandan Qian•Ye Cong•Runhao Wang•Quan Chen•Chuangye Yan等 6 人
Nature Communications
2023
•2023/6/15
•Vol.14 No.1 p.1-10
The systemic RNAi-defective (SID) transmembrane family member 2 (SIDT2) is a putative nucleic acid channel or transporter that plays essential roles in nucleic acid transport and lipid metabolism. Here, we report the cryo-electron microscopy (EM) structures of human SIDT2, which forms a tightly pack...
Cryoelectron microscopyEnzyme mechanismsHydrolasesMembrane proteins
10.1038/S41467-023-39335-2
ISSN:2041-1723
Structures of the mumps virus polymerase complex via cryo-electron microscopy
Tianhao Li•Mingdong Liu•Zhanxi Gu•Xin Su•Yunhui Liu等 8 人
Nature Communications
2024
•2024/5/17
•Vol.15 No.1 p.1-12
The viral polymerase complex, comprising the large protein (L) and phosphoprotein (P), is crucial for both genome replication and transcription in non-segmented negative-strand RNA viruses (nsNSVs), while structures corresponding to these activities remain obscure. Here, we resolved two L–P complex ...
Cryoelectron microscopyVirus structures
10.1038/S41467-024-48389-9
ISSN:2041-1723
NEDAMSS syndrome-related truncating and missense mutations are associated with aberrant liquid-liquid phase separation of IRF2BPL
Marco Dell’Oca•Stefania Boggio Bozzo•Serena Vaglietti•Chiara Marchetti•Chiara Di Luca等 33 人
Nature Communications
2026
•2026/2/27
•Vol.17 No.1 p.33010
Since 2018, truncating and missense mutations in the IRF2BPL gene have been associated with the neurodevelopmental NEDAMSS syndrome and other IRF2BPL-related disorders. These mutations mainly affect the gene region encoding the central portion of the IRF2BPL protein, whose physiopathological roles a...
Intrinsically disordered proteinsProtein aggregation
10.1038/S41467-026-69781-7
ISSN:2041-1723
Structural basis for the catalytic mechanism of human lipid phosphate phosphatases
Meng Yang•Chunping Sun•Yonglin He•Hongwu Qian
Nature Chemical Biology
2026
•2026/1/9
•00 p.1-9
Lipid phosphate phosphatases (LPPs) catalyze the dephosphorylation of a broad range of bioactive lipid phosphates, including lysophosphatidic acid and sphingosine-1-phosphate, playing essential roles in embryonic vasculogenesis, cell differentiation and inflammation. Here we present the cryo-electro...
BiocatalysisPhospholipidsStructural biology
10.1038/S41589-025-02121-W
ISSN:1552-4450
Structural basis for directional chitin biosynthesis
Chen Wei•Cao Peng•Liu Yuansheng•Yu Ailing•Wang Dong等 11 人
Nature
2022
•2022/9/21
•Vol.610 No.7931 p.402-408
Chitin, the most abundant aminopolysaccharide in nature, is an extracellular polymer consisting of N-acetylglucosamine (GlcNAc) units1. The key reactions of chitin biosynthesis are catalysed by chitin synthase2–4, a membrane-integrated glycosyltransferase that transfers GlcNAc from UDP-GlcNAc to a g...
Cryoelectron microscopyTransferases
10.1038/S41586-022-05244-5
ISSN:0028-0836
Orthosteric STING inhibition elucidates molecular correction of SAVI STING
Tao Xie•Max Ruzanov•David Critton•Leidy Merselis•Joseph Naglich等 18 人
Nature Communications
2025
•2025/7/1
•Vol.16 No.1 p.1-14
While the progression of STING activators into the clinic has been successful, the discovery and clinical progression of STING inhibitors remain elusive. Questions persist about the molecular properties needed to distinguish between a STING activator and inhibitor, particularly within SAVI disease, ...
Immunological techniquesInnate immunitySolution-state NMRX-ray crystallography
10.1038/S41467-025-60632-5
ISSN:2041-1723
PLMSearch: Protein language model powers accurate and fast sequence search for remote homology
Wei Liu•Ziye Wang•Ronghui You•Chenghan Xie•Hong Wei等 8 人
Nature Communications
2024
•2024/3/30
•Vol.15 No.1 p.1-12
Homologous protein search is one of the most commonly used methods for protein annotation and analysis. Compared to structure search, detecting distant evolutionary relationships from sequences alone remains challenging. Here we propose PLMSearch (Protein Language Model), a homologous protein search...
BioinformaticsComputational modelsProtein sequence analysesProtein sequencingSoftware
10.1038/S41467-024-46808-5
ISSN:2041-1723
The structure of Arabidopsis phytochrome A reveals topological and functional diversification among the plant photoreceptor isoforms
E. Sethe Burgie•Hua Li•Zachary T. K. Gannam•Katrice E. McLoughlin•Richard D. Vierstra等 6 人
Nature Plants
2023
•2023/6/8
•00 p.1-14
Plants employ a divergent cohort of phytochrome (Phy) photoreceptors to govern many aspects of morphogenesis through reversible photointerconversion between inactive Pr and active Pfr conformers. The two most influential are PhyA whose retention of Pfr enables sensation of dim light, while the relat...
Cryoelectron microscopyLight responsesPlant signallingStructure determination
10.1038/S41477-023-01435-8
ISSN:2055-0278
An engineered hypercompact CRISPR-Cas12f system with boosted gene-editing activity
Tong Wu•Chang Liu•Siyuan Zou•Ruitu Lyu•Bowei Yang等 8 人
Nature Chemical Biology
2023
•2023/7/3
•00 p.1-10
Compact CRISPR-Cas systems offer versatile treatment options for genetic disorders, but their application is often limited by modest gene-editing activity. Here we present enAsCas12f, an engineered RNA-guided DNA endonuclease up to 11.3-fold more potent than its parent protein, AsCas12f, and one-thi...
Protein designSynthetic biology
10.1038/S41589-023-01380-9
ISSN:1552-4450
Microfluidics combined with electron microscopy for rapid and high-throughput mapping of antibody–viral glycoprotein complexes
Leigh M. Sewall•Rebeca de Paiva Froes Rocha•Grace Gibson•Michelle Louie•Zhenfei Xie等 17 人
Nature Biomedical Engineering
2025
•2025/6/3
•00 p.1-14
Understanding the mechanistic interplay between antibodies and invading pathogens is essential for vaccine development. Current methods are labour and time intensive and limited by sample preparation bottlenecks. Here we present microfluidic electron microscopy-based polyclonal epitope mapping (mEM)...
Cryoelectron microscopyMicrofluidicsVaccines
10.1038/S41551-025-01411-X
ISSN:2157-846X
Enzymatic catalysis favours eight-membered over five-membered ring closure in bicyclomycin biosynthesis
Jun-Bin He•Lian Wu•Wanqing Wei•Song Meng•Zheng-Tao Liu等 11 人
Nature Catalysis
2023
•2023/7/17
•Vol.6 No.7 p.637-648
The construction of O-heterocycles is an important step in organic synthesis and biosynthesis for producing valuable ring compounds. Although enzyme-catalysed five- or six-membered ring closures in O-heterocycle biosynthesis have been studied extensively, the enzymatic formation of eight-membered O-...
BiocatalysisBiosynthesisEnzyme mechanisms
10.1038/S41929-023-00987-4
ISSN:2520-1158
Structural basis of coronavirus E protein interactions with human PALS1 PDZ domain
Airah Javorsky•Patrick O. Humbert•Marc Kvansakul
Communications Biology
2021
•2021/6/11
•Vol.4 No.1 p.1-8
SARS-CoV-2 infection leads to coronavirus disease 2019 (COVID-19), which is associated with severe and life-threatening pneumonia and respiratory failure. However, the molecular basis of these symptoms remains unclear. SARS-CoV-1 E protein interferes with control of cell polarity and cell-cell junct...
SARS-CoV-2X-ray crystallography
10.1038/S42003-021-02250-7
ISSN:2399-3642
Illuminating protein space with a programmable generative model
John B. Ingraham•Max Baranov•Zak Costello•Karl W. Barber•Wujie Wang等 26 人
Nature
2023
•2023/11/15
•00 p.1-9
Three billion years of evolution has produced a tremendous diversity of protein molecules1, but the full potential of proteins is likely to be much greater. Accessing this potential has been challenging for both computation and experiments because the space of possible protein molecules is much larg...
Machine learningProtein design
10.1038/S41586-023-06728-8
ISSN:0028-0836
Cryo-EM structure and oligomerization of the human planar cell polarity core protein Vangl1
Fan Zhang•Shaobai Li•Hao Wu•Shanshuang Chen
Nature Communications
2025
•2025/1/3
•Vol.16 No.1 p.1-11
Vangl is a planar cell polarity (PCP) core protein essential for aligned cell orientation along the epithelial plane perpendicular to the apical-basal direction, which is important for tissue morphogenesis, development and collective cell behavior. Mutations in Vangl are associated with developmenta...
Cell polarityCryoelectron microscopyMembrane proteins
10.1038/S41467-024-55397-2
ISSN:2041-1723
Serine hydroxymethyltransferase as a potential target of antibacterial agents acting synergistically with one-carbon metabolism-related inhibitors
Makino Yuko•Oe Chihiro•Iwama Kazuya•Suzuki Satoshi•Nishiyama Akie等 19 人
Communications Biology
2022
•2022/6/23
•Vol.5 No.1 p.1-12
Serine hydroxymethyltransferase (SHMT) produces 5,10-methylenetetrahydrofolate (CH2-THF) from tetrahydrofolate with serine to glycine conversion. SHMT is a potential drug target in parasites, viruses and cancer. (+)-SHIN-1 was developed as a human SHMT inhibitor for cancer therapy. However, the pote...
Target identificationX-ray crystallography
10.1038/S42003-022-03555-X
ISSN:2399-3642
Gastric proton pump with two occluded K+ engineered with sodium pump-mimetic mutations
Abe Kazuhiro•Yamamoto Kenta•Irie Katsumasa•Nishizawa Tomohiro•Oshima Atsunori
Nature Communications
2021
•2021/9/29
•Vol.12 No.1 p.1-11
The gastric H+,K+-ATPase mediates electroneutral exchange of 1H+/1K+ per ATP hydrolysed across the membrane. Previous structural analysis of the K+-occluded E2-P transition state of H+,K+-ATPase showed a single bound K+ at cation-binding site II, in marked contrast to the two K+ ions occluded at sit...
BioenergeticsCryoelectron microscopyX-ray crystallography
10.1038/S41467-021-26024-1
ISSN:2041-1723
Deciphering the molecular mechanism of the bacterial division motor TolQRA
Chongrong Shen•Teng Xie•Yongbo Luo•Fangyuan Zhao•Xin Wang等 17 人
Cell Discovery
2025
•2025/11/4
•Vol.11 No.1 p.1-12
The Tol-Pal system is essential for maintaining outer membrane (OM) stability during cell division in Gram-negative bacteria. The inner membrane complex TolQRA harnesses proton motive force (PMF) to establish transient interactions within the periplasm, thereby coordinating cell envelope remodeling ...
Cell divisionCryoelectron microscopy
10.1038/S41421-025-00841-W
ISSN:2056-5968
Computational stabilization of T cell receptors allows pairing with antibodies to form bispecifics
Karen Froning•Jack Maguire•Arlene Sereno•Flora Huang•Shawn Chang等 17 人
Nature Communications
2020
•2020/5/11
•Vol.11 No.1 p.1-14
Recombinant T cell receptors (TCRs) can be used to redirect naïve T cells to eliminate virally infected or cancerous cells; however, they are plagued by low stability and uneven expression. Here, we use molecular modeling to identify mutations in the TCR constant domains (Cα/Cβ) that increase the un...
Adaptive immunityBiochemistryCancerImmunotherapyTumour immunology
10.1038/S41467-020-16231-7
ISSN:2041-1723
Structural insights into ion selectivity and transport mechanisms of Oryza sativa HKT2;1 and HKT2;2/1 transporters
Xiaohui Wang•Xiaoshuai Shen•Yannan Qu•Heng Zhang•Chu Wang等 7 人
Nature Plants
2024
•2024/4/3
•00 p.1-12
Plant high-affinity K+ transporters (HKTs) play a pivotal role in maintaining the balance of Na+ and K+ ions in plants, thereby influencing plant growth under K+-depleted conditions and enhancing tolerance to salinity stress. Here we report the cryo-electron microscopy structures of Oryza sativa HKT...
Plant molecular biologyPlant stress responses
10.1038/S41477-024-01665-4
ISSN:2055-0278
The GATE glycoprotein complex enhances human cytomegalovirus entry in endothelial cells
Michael J. Norris•Lauren A. Henderson•Mohammed N. A. Siddiquey•Jieyun Yin•Kwangsun Yoo等 10 人
Nature Microbiology
2025
•2025/6/30
•Vol.10 No.7 p.1605-1616
Human cytomegalovirus can cause severe birth defects upon infection in pregnant women and complications in immunocompromised patients. A major challenge for vaccine design is our incomplete understanding of the diverse protein complexes this virus uses to infect cells. In Herpesviridae, glycoprotein...
Cryoelectron microscopyHerpes virusViral infection
10.1038/S41564-025-02025-4
ISSN:2058-5276
Design of facilitated dissociation enables timing of cytokine signalling
Adam J. Broerman•Christoph Pollmann•Yang Zhao•Mauriz A. Lichtenstein•Mark D. Jackson等 22 人
Nature
2025
•2025/9/24
•00 p.1-8
Protein design has focused on the design of ground states, ensuring that they are sufficiently low energy to be highly populated1. Designing the kinetics and dynamics of a system requires, in addition, the design of excited states that are traversed in transitions from one low-lying state to another...
Deformation dynamicsInterleukinsKineticsProtein designX-ray crystallography
10.1038/S41586-025-09549-Z
ISSN:0028-0836
Fast, accurate antibody structure prediction from deep learning on massive set of natural antibodies
Ruffolo Jeffrey A.•Chu Lee-Shin•Mahajan Sai Pooja•Gray Jeffrey J.
Nature Communications
2023
•2023/4/25
•Vol.14 No.1 p.1-13
Antibodies have the capacity to bind a diverse set of antigens, and they have become critical therapeutics and diagnostic molecules. The binding of antibodies is facilitated by a set of six hypervariable loops that are diversified through genetic recombination and mutation. Even with recent advances...
Machine learningMolecular modellingProtein databasesProtein structure predictions
10.1038/S41467-023-38063-X
ISSN:2041-1723
Crowded environments tune the fold-switching in metamorphic proteins
Ning Zhang•Wenyan Guan•Shouqi Cui•Nana Ai
Communications Chemistry
2023
•2023/6/8
•Vol.6 No.1 p.1-7
Metamorphic proteins such as circadian clock protein KaiB and human chemokine XCL1 play vital roles in regulating biological processes, including gene expression, circadian clock and innate immune responses, and perform distinct functions in living cell by switching different structures in response ...
Biophysical chemistryCircadian rhythm signalling peptides and proteinsProtein foldingSolution-state NMR
10.1038/S42004-023-00909-2
ISSN:2399-3669
Support field neural representation learner framework for learning stability landscapes in molecular geometry
Jianshi WANG
Npj Biomedical Innovations
2025
•2025/11/26
•Vol.2 No.1 p.420
Understanding the determinants of protein structural stability remains a central challenge in computational biology. While recent prediction models achieve high accuracy, they provide limited insight into why specific conformations persist or how topology and packing confer robustness. We introduce ...
BiophysicsComputational biology and bioinformaticsMathematics and computingPhysics
10.1038/S44385-025-00045-7
ISSN:3005-1444
A multi-factor trafficking site on the spliceosome remodeling enzyme BRR2 recruits C9ORF78 to regulate alternative splicing
Bergfort Alexandra•Preußner Marco•Kuropka Benno•Ilik İbrahim Avşar•Hilal Tarek等 10 人
Nature Communications
2022
•2022/3/3
•Vol.13 No.1 p.1-16
The intrinsically unstructured C9ORF78 protein was detected in spliceosomes but its role in splicing is presently unclear. We find that C9ORF78 tightly interacts with the spliceosome remodeling factor, BRR2, in vitro. Affinity purification/mass spectrometry and RNA UV-crosslinking analyses identify ...
Alternative splicingCryoelectron microscopy
10.1038/S41467-022-28754-2
ISSN:2041-1723
Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions
Georg Krainer•Timothy J. Welsh•Jerelle A. Joseph•Jorge R. Espinosa•Sina Wittmann等 19 人
Nature Communications
2021
•2021/2/17
•Vol.12 No.1 p.1-14
Liquid–liquid phase separation of proteins underpins the formation of membraneless compartments in living cells. Elucidating the molecular driving forces underlying protein phase transitions is therefore a key objective for understanding biological function and malfunction. Here we show that cellula...
Biological physicsBiophysical chemistryBiophysicsIntrinsically disordered proteinsProteins
10.1038/S41467-021-21181-9
ISSN:2041-1723
Transcription factors modulate RNA polymerase conformational equilibrium
Zhu Chengjin•Guo Xieyang•Dumas Philippe•Takacs Maria•Abdelkareem Mo’men等 11 人
Nature Communications
2022
•2022/3/22
•Vol.13 No.1 p.1-12
RNA polymerase (RNAP) frequently pauses during the transcription of DNA to RNA to regulate gene expression. Transcription factors NusA and NusG modulate pausing, have opposing roles, but can bind RNAP simultaneously. Here we report cryo-EM reconstructions of Escherichia coli RNAP bound to NusG, or N...
Cryoelectron microscopyEnzyme mechanismsTranscriptional regulatory elements
10.1038/S41467-022-29148-0
ISSN:2041-1723
Antiviral HIV-1 SERINC restriction factors disrupt virus membrane asymmetry
Susan A. Leonhardt•Michael D. Purdy•Jonathan R. Grover•Ziwei Yang•Sandra Poulos等 18 人
Nature Communications
2023
•2023/7/20
•Vol.14 No.1 p.1-16
The host proteins SERINC3 and SERINC5 are HIV-1 restriction factors that reduce infectivity when incorporated into the viral envelope. The HIV-1 accessory protein Nef abrogates incorporation of SERINCs via binding to intracellular loop 4 (ICL4). Here, we determine cryoEM maps of full-length human SE...
Antimicrobial responsesCryoelectron microscopyTranslational researchVirus–host interactions
10.1038/S41467-023-39262-2
ISSN:2041-1723
Antiviral type III CRISPR signalling via conjugation of ATP and SAM
Haotian Chi•Ville Hoikkala•Sabine Grüschow•Shirley Graham•Sally Shirran等 6 人
Nature
2023
•2023/10/18
•00 p.1-8
CRISPR systems are widespread in the prokaryotic world, providing adaptive immunity against mobile genetic elements1,2. Type III CRISPR systems, with the signature gene cas10, use CRISPR RNA to detect non-self RNA, activating the enzymatic Cas10 subunit to defend the cell against mobile genetic elem...
BacteriaBacteriophagesEnzyme mechanismsRNA
10.1038/S41586-023-06620-5
ISSN:0028-0836
Structure and assembly of the dystrophin glycoprotein complex
Li Wan•Xiaofei Ge•Qikui Xu•Gaoxingyu Huang•Tiandi Yang等 8 人
Nature
2024
•2024/12/11
•00 p.1-9
The dystrophin glycoprotein complex (DGC) has a crucial role in maintaining cell membrane stability and integrity by connecting the intracellular cytoskeleton with the surrounding extracellular matrix1–3. Dysfunction of dystrophin and its associated proteins results in muscular dystrophy, a disorder...
Cryoelectron microscopyMechanotransductionMembrane structure and assembly
10.1038/S41586-024-08310-2
ISSN:0028-0836
Dynamic assemblies and coordinated reactions of non-homologous end joining
Lan Liu•Jun Li•Metztli Cisneros-Aguirre•Arianna Merkell•Jeremy M. Stark等 7 人
Nature
2025
•2025/6/11
•00 p.1-8
Non-homologous end joining (NHEJ) is the main repair pathway of double-strand DNA breaks in higher eukaryotes1,2. Here we report reconstitution of the final steps of NHEJ and structures of DNA polymerase μ and ligase IV (LIG4) engaged in gap filling and end joining. These reactions take place in a f...
Electron microscopyEnzyme mechanismsNon-homologous-end joining
10.1038/S41586-025-09078-9
ISSN:0028-0836
LassoPred: a tool to predict the 3D structure of lasso peptides
Xingyu Ouyang•Xinchun Ran•Han Xu•Runeem Al-Abssi•Yi-Lei Zhao等 7 人
Nature Communications
2025
•2025/7/1
•Vol.16 No.1 p.1-13
Lasso peptides (LaPs), characterized by their entangled slipknot-like structures, are a large class of ribosomally synthesized and post-translationally modified peptides (RiPPs), with examples functioning as antibiotics, enzyme inhibitors, and molecular switches. Despite thousands of LaP sequences p...
BiochemistryDatabasesStructural biology
10.1038/S41467-025-60544-4
ISSN:2041-1723
Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses
Schulz Rouven•Korkut-Demirbaş Medina•Venturino Alessandro•Colombo Gloria•Siegert Sandra
Nature Communications
2022
•2022/8/15
•Vol.13 No.1 p.1-26
G protein-coupled receptors (GPCRs) regulate processes ranging from immune responses to neuronal signaling. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additionally, dissecting cell type-specific responses is challenging when the same ...
Cell signallingMicrogliaNeuroimmunologySynthetic biology
10.1038/S41467-022-32390-1
ISSN:2041-1723
Cas1 mediates the interference stage in a phage-encoded CRISPR–Cas system
Laixing Zhang•Hao Wang•Jianwei Zeng•Xueli Cao•Zhengyu Gao等 11 人
Nature Chemical Biology
2024
•2024/7/8
•00 p.1-11
Clustered regularly interspaced short palindromic repeats (CRISPR)–Cas systems are prokaryotic adaptive immune systems against invading phages and other mobile genetic elements. Notably, some phages, including the Vibrio cholerae-infecting ICP1 (International Center for Diarrheal Disease Research, B...
Chemical biologyStructural biology
10.1038/S41589-024-01659-5
ISSN:1552-4450
Functional spectrum and specificity of mitochondrial ferredoxins FDX1 and FDX2
Schulz Vinzent•Basu Somsuvro•Freibert Sven-A.•Webert Holger•Boss Linda等 12 人
Nature Chemical Biology
2022
•2022/10/24
•Vol.19 No.2 p.206-217
Ferredoxins comprise a large family of iron–sulfur (Fe–S) proteins that shuttle electrons in diverse biological processes. Human mitochondria contain two isoforms of [2Fe-2S] ferredoxins, FDX1 (aka adrenodoxin) and FDX2, with known functions in cytochrome P450-dependent steroid transformations and F...
BiocatalysisEnzyme mechanismsMetalsX-ray crystallography
10.1038/S41589-022-01159-4
ISSN:1552-4450
The architecture of substrate-engaged TOM–TIM23 supercomplex reveals preprotein proximity sites for mitochondrial protein translocation
Qiang Wang•Jinjin Zhuang•Rui Huang•Zeyuan Guan•Ling Yan等 10 人
Cell Discovery
2024
•2024/2/16
•Vol.10 No.1 p.1-4
Cryoelectron microscopyProtein translocation
10.1038/S41421-023-00643-Y
ISSN:2056-5968
Cryo-EM structure and dynamics of eukaryotic DNA polymerase δ holoenzyme
Rinku Jain•William J. Rice•Radhika Malik•Robert E. Johnson•Louise Prakash等 8 人
Nature Structural & Molecular Biology
2019
•2019/10/3
•Vol.26 No.10 p.955-962
DNA polymerase δ (Polδ) plays pivotal roles in eukaryotic DNA replication and repair. Polδ is conserved from yeast to humans, and mutations in human Polδ have been implicated in various cancers. Saccharomyces cerevisiae Polδ consists of catalytic Pol3 and the regulatory Pol31 and Pol32 subunits. Her...
Cryoelectron microscopyDNA synthesis
10.1038/S41594-019-0305-Z
ISSN:1545-9993
Bromodomain factor 5 is an essential regulator of transcription in Leishmania
Jones Nathaniel G.•Geoghegan Vincent•Moore Gareth•Carnielli Juliana B. T.•Newling Katherine等 12 人
Nature Communications
2022
•2022/7/13
•Vol.13 No.1 p.1-18
Leishmania are unicellular parasites that cause human and animal diseases. Like other kinetoplastids, they possess large transcriptional start regions (TSRs) which are defined by histone variants and histone lysine acetylation. Cellular interpretation of these chromatin marks is not well understood....
ChromatinGene expressionParasite biologyTranscription
10.1038/S41467-022-31742-1
ISSN:2041-1723
Plant phytochrome B is an asymmetric dimer with unique signalling potential
Li Hua•Burgie E. Sethe•Gannam Zachary T. K.•Li Huilin•Vierstra Richard D.
Nature
2022
•2022/3/30
•00 p.1-7
Many aspects of plant photoperception are mediated by the phytochrome (Phy) family of bilin-containing photoreceptors that reversibly interconvert between inactive Pr and active Pfr conformers1,2. Despite extensive biochemical studies, full understanding of plant Phy signalling has remained unclear ...
Cryoelectron microscopyLight responses
10.1038/S41586-022-04529-Z
ISSN:0028-0836
Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant
Jumpei Ito•Rigel Suzuki•Keiya Uriu•Yukari Itakura•Jiri Zahradnik等 39 人
Nature Communications
2023
•2023/5/11
•Vol.14 No.1 p.1-20
In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvar...
SARS-CoV-2Virus–host interactions
10.1038/S41467-023-38188-Z
ISSN:2041-1723
RBD-depleted SARS-CoV-2 spike generates protective immunity in cynomolgus macaques
Hélène Letscher•Delphine Guilligay•Gregory Effantin•Axelle Amen•Guidenn Sulbaran等 22 人
Npj Vaccines
2025
•2025/3/30
•Vol.10 No.1 p.1-16
The SARS-CoV-2 pandemic revealed the rapid evolution of circulating strains. This led to new variants carrying mostly mutations within the receptor binding domain, which is immunodominant upon immunization and infection. In order to steer the immune response away from RBD epitopes to more conserved ...
BiotechnologyDiseasesImmunology
10.1038/S41541-025-01113-0
ISSN:2059-0105
Structure of a microtubule-bound axonemal dynein
Travis Walton•Hao Wu•Alan Brown
Nature Communications
2021
•2021/1/20
•Vol.12 No.1 p.1-9
Axonemal dyneins are tethered to doublet microtubules inside cilia to drive ciliary beating, a process critical for cellular motility and extracellular fluid flow. Axonemal dyneins are evolutionarily and biochemically distinct from cytoplasmic dyneins that transport cargo, and the mechanisms regulat...
CiliaCryoelectron microscopyDynein
10.1038/S41467-020-20735-7
ISSN:2041-1723
Identifying a key spot for electron mediator-interaction to tailor CO dehydrogenase’s affinity
Suk Min Kim•Sung Heuck Kang•Jinhee Lee•Yoonyoung Heo•Eleni G. Poloniataki等 13 人
Nature Communications
2024
•2024/3/28
•Vol.15 No.1 p.1-12
Fe‒S cluster-harboring enzymes, such as carbon monoxide dehydrogenases (CODH), employ sophisticated artificial electron mediators like viologens to serve as potent biocatalysts capable of cleaning-up industrial off-gases at stunning reaction rates. Unraveling the interplay between these enzymes and ...
BiocatalysisEnzyme mechanismsEnzymesX-ray crystallography
10.1038/S41467-024-46909-1
ISSN:2041-1723
Microbial production of megadalton titin yields fibers with advantageous mechanical properties
Bowen Christopher H.•Sargent Cameron J.•Wang Ao•Zhu Yaguang•Chang Xinyuan等 11 人
Nature Communications
2021
•2021/8/30
•Vol.12 No.1 p.1-12
Manmade high-performance polymers are typically non-biodegradable and derived from petroleum feedstock through energy intensive processes involving toxic solvents and byproducts. While engineered microbes have been used for renewable production of many small molecules, direct microbial synthesis of ...
Bioinspired materialsBiomaterials – proteinsBiopolymersProteinsSynthetic biology
10.1038/S41467-021-25360-6
ISSN:2041-1723
Rapid protein assignments and structures from raw NMR spectra with the deep learning technique ARTINA
Klukowski Piotr•Riek Roland•Güntert Peter
Nature Communications
2022
•2022/10/18
•Vol.13 No.1 p.1-12
Nuclear Magnetic Resonance (NMR) spectroscopy is a major technique in structural biology with over 11,800 protein structures deposited in the Protein Data Bank. NMR can elucidate structures and dynamics of small and medium size proteins in solution, living cells, and solids, but has been limited by ...
Machine learningSolution-state NMR
10.1038/S41467-022-33879-5
ISSN:2041-1723
De novo generation of multi-target compounds using deep generative chemistry
Brenton P. Munson•Michael Chen•Audrey Bogosian•Jason F. Kreisberg•Katherine Licon等 8 人
Nature Communications
2024
•2024/5/6
•Vol.15 No.1 p.1-12
Polypharmacology drugs—compounds that inhibit multiple proteins—have many applications but are difficult to design. To address this challenge we have developed POLYGON, an approach to polypharmacology based on generative reinforcement learning. POLYGON embeds chemical space and iteratively samples i...
Computational modelsDrug developmentDrug discoveryMachine learning
10.1038/S41467-024-47120-Y
ISSN:2041-1723
The role of G protein conformation in receptor–G protein selectivity
Jang Wonjo•Lu Sumin•Xu Xin•Wu Guangyu•Lambert Nevin A.
Nature Chemical Biology
2023
•2023/1/16
•00 p.1-8
G protein-coupled receptors (GPCRs) selectively activate at least one of the four families of heterotrimeric G proteins, but the mechanism of coupling selectivity remains unclear. Structural studies emphasize structural complementarity of GPCRs and nucleotide-free G proteins, but selectivity is like...
Cell signallingChemical toolsG protein-coupled receptorsPharmacology
10.1038/S41589-022-01231-Z
ISSN:1552-4450
Machine learning coarse-grained potentials of protein thermodynamics
Maciej Majewski•Adrià Pérez•Philipp Thölke•Stefan Doerr•Nicholas E. Charron等 10 人
Nature Communications
2023
•2023/9/15
•Vol.14 No.1 p.1-13
A generalized understanding of protein dynamics is an unsolved scientific problem, the solution of which is critical to the interpretation of the structure-function relationships that govern essential biological processes. Here, we approach this problem by constructing coarse-grained molecular poten...
Machine learningMolecular dynamicsMolecular modellingProtein analysisProtein function predictions
10.1038/S41467-023-41343-1
ISSN:2041-1723
Modular assembly of an artificially concise biocatalytic cascade for the manufacture of phenethylisoquinoline alkaloids
Yue Gao•Fei Li•Zhengshan Luo•Zhiwei Deng•Yan Zhang等 8 人
Nature Communications
2024
•2024/1/2
•Vol.15 No.1 p.1-13
Plant-derived alkaloids are an important class of pharmaceuticals. However, they still rely on phytoextraction to meet their diverse market demands. Since multistep biocatalytic cascades have begun to revolutionize the manufacture of natural or unnatural products, to address the synthetic challenges...
BiocatalysisNatural productsProtein engineeringSynthetic biology
10.1038/S41467-023-44420-7
ISSN:2041-1723
The δ subunit and NTPase HelD institute a two-pronged mechanism for RNA polymerase recycling
Hao-Hong Pei•Tarek Hilal•Zhuo A. Chen•Yong-Heng Huang•Yuan Gao等 11 人
Nature Communications
2020
•2020/12/18
•Vol.11 No.1 p.1-14
Cellular RNA polymerases (RNAPs) can become trapped on DNA or RNA, threatening genome stability and limiting free enzyme pools, but how RNAP recycling into active states is achieved remains elusive. In Bacillus subtilis, the RNAP δ subunit and NTPase HelD have been implicated in RNAP recycling. We s...
Cryoelectron microscopyEnzyme mechanismsTranscriptionTranscription factors
10.1038/S41467-020-20159-3
ISSN:2041-1723
C. elegans germ granules require both assembly and localized regulators for mRNA repression
Scott Takeo Aoki•Tina R. Lynch•Sarah L. Crittenden•Craig A. Bingman•Marvin Wickens等 6 人
Nature Communications
2021
•2021/2/12
•Vol.12 No.1 p.1-14
Cytoplasmic RNA–protein (RNP) granules have diverse biophysical properties, from liquid to solid, and play enigmatic roles in RNA metabolism. Nematode P granules are paradigmatic liquid droplet granules and central to germ cell development. Here we analyze a key P granule scaffolding protein, PGL-1,...
BiochemistryGene regulationGermline developmentRNARNA metabolism
10.1038/S41467-021-21278-1
ISSN:2041-1723
Elucidation of the structural basis for ligand binding and translocation in conserved insect odorant receptor co-receptors
Jody Pacalon•Guillaume Audic•Justine Magnat•Manon Philip•Jérôme Golebiowski等 7 人
Nature Communications
2023
•2023/12/11
•Vol.14 No.1 p.1-11
In numerous insects, the olfactory receptor family forms a unique class of heteromeric cation channels. Recent progress in resolving the odorant receptor structures offers unprecedented opportunities for deciphering their molecular mechanisms of ligand recognition. Unexpectedly, these structures in ...
BioinformaticsComputational chemistryLigand-gated ion channelsMolecular dynamicsPatch clamp
10.1038/S41467-023-44058-5
ISSN:2041-1723
Synergy between Winter Flounder antimicrobial peptides
Maria Clarke•Charlotte K. Hind•Philip M. Ferguson•Giorgia Manzo•Bhumil Mistry等 13 人
Npj Antimicrobials And Resistance
2023
•2023/8/10
•Vol.1 No.1 p.1-16
Some antimicrobial peptides (AMPs) have potent bactericidal activity and are being considered as potential alternatives to classical antibiotics. In response to an infection, such AMPs are often produced in animals alongside other peptides with low or no perceivable antimicrobial activity, whose rol...
AntibioticsComputational modelsPeptidesPharmacodynamics
10.1038/S44259-023-00010-7
ISSN:2731-8745
Structures of ACE2–SIT1 recognized by Omicron variants of SARS-CoV-2
Shen Yaping•Wang Jianhui•Li Yaning•Zhang Yuanyuan•Tian Ruilin等 6 人
Cell Discovery
2022
•2022/11/16
•Vol.8 No.1 p.1-4
Cryoelectron microscopyMechanisms of disease
10.1038/S41421-022-00488-X
ISSN:2056-5968
Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain
Bo Liu•Honghui Liu•Pu Han•Xiaoyun Wang•Chunmei Wang等 15 人
Signal Transduction And Targeted Therapy
2024
•2024/5/13
•Vol.9 No.1 p.1-12
Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged or emerging variants, such as Omicron and its sub-variants. This suggests that highly co...
ImmunotherapyInfectious diseases
10.1038/S41392-024-01847-8
ISSN:2059-3635
Structures of autoinhibited and polymerized forms of CARD9 reveal mechanisms of CARD9 and CARD11 activation
Michael J. Holliday•Axel Witt•Alejandro Rodríguez Gama•Benjamin T. Walters•Christopher P. Arthur等 9 人
Nature Communications
2019
•2019/7/11
•Vol.10 No.1 p.1-17
CARD9 and CARD11 drive immune cell activation by nucleating Bcl10 polymerization, but are held in an autoinhibited state prior to stimulation. Here, we elucidate the structural basis for this autoinhibition by determining the structure of a region of CARD9 that includes an extensive interface betwee...
Cryoelectron microscopyProteinsSolution-state NMR
10.1038/S41467-019-10953-Z
ISSN:2041-1723
Genome mining unveils a class of ribosomal peptides with two amino termini
Ren Hengqian•Dommaraju Shravan R.•Huang Chunshuai•Cui Haiyang•Pan Yuwei等 10 人
Nature Communications
2023
•2023/3/23
•Vol.14 No.1 p.1-13
The era of inexpensive genome sequencing and improved bioinformatics tools has reenergized the study of natural products, including the ribosomally synthesized and post-translationally modified peptides (RiPPs). In recent years, RiPP discovery has challenged preconceptions about the scope of post-tr...
BioinformaticsBiosynthesisEnzymesNatural product synthesis
10.1038/S41467-023-37287-1
ISSN:2041-1723
Molecular basis of human noradrenaline transporter reuptake and inhibition
Jiaxin Tan•Yuan Xiao•Fang Kong•Xiaochun Zhang•Hanwen Xu等 11 人
Nature
2024
•2024/7/24
•00 p.1-9
Noradrenaline, also known as norepinephrine, has a wide range of activities and effects on most brain cell types1. Its reuptake from the synaptic cleft heavily relies on the noradrenaline transporter (NET) located in the presynaptic membrane2. Here we report the cryo-electron microscopy (cryo-EM) st...
Cryoelectron microscopyDiseases of the nervous system
10.1038/S41586-024-07719-Z
ISSN:0028-0836
Self-assembling nanoparticle engineered from the ferritinophagy complex as a rabies virus vaccine candidate
Dan Fu•Wenming Wang•Yan Zhang•Fan Zhang•Pinyi Yang等 15 人
Nature Communications
2024
•2024/10/4
•Vol.15 No.1 p.1-21
Over the past decade, there has been a growing interest in ferritin-based vaccines due to their enhanced antigen immunogenicity and favorable safety profiles, with several vaccine candidates targeting various pathogens advancing to phase I clinical trials. Nevertheless, challenges associated with pa...
Protein vaccinesStructural biologyViral infection
10.1038/S41467-024-52908-Z
ISSN:2041-1723
Efficient reductive desymmetrization of bulky 1,3-cyclodiketones enabled by structure-guided directed evolution of a carbonyl reductase
Xi Chen•Hongliu Zhang•Miguel A. Maria-Solano•Weidong Liu•Juan Li等 12 人
Nature Catalysis
2019
•2019/10/7
•Vol.2 No.10 p.931-941
Reductive desymmetrization of 2,2-disubstituted prochiral 1,3-cyclodiketones to 2,2-disubstituted-3-hydroxycycloketones is a highly desired transformation for the construction of complex molecules with multiple chiral centres, but the generation of a single stereoisomer is difficult and an extremely...
Asymmetric catalysisBiocatalysisOxidoreductasesChemical synthesis
10.1038/S41929-019-0347-Y
ISSN:2520-1158
Mre11-Rad50 oligomerization promotes DNA double-strand break repair
Kissling Vera M.•Reginato Giordano•Bianco Eliana•Kasaciunaite Kristina•Tilma Janny等 13 人
Nature Communications
2022
•2022/5/2
•Vol.13 No.1 p.1-16
The conserved Mre11-Rad50 complex is crucial for the detection, signaling, end tethering and processing of DNA double-strand breaks. While it is known that Mre11-Rad50 foci formation at DNA lesions accompanies repair, the underlying molecular assembly mechanisms and functional implications remained ...
Confocal microscopyDouble-strand DNA breaksNucleasesSingle-molecule biophysicsTransmission electron microscopy
10.1038/S41467-022-29841-0
ISSN:2041-1723
Near-atomic structure of the inner ring of the Saccharomyces cerevisiae nuclear pore complex
Li Zongqiang•Chen Shuaijiabin•Zhao Liang•Huang Guoqiang•Pi Xiong等 8 人
Cell Research
2022
•2022/3/18
•00 p.1-14
Nuclear pore complexes (NPCs) mediate bidirectional nucleocytoplasmic transport of substances in eukaryotic cells. However, the accurate molecular arrangement of NPCs remains enigmatic owing to their huge size and highly dynamic nature. Here we determined the structure of the asymmetric unit of the ...
Cryoelectron microscopyNuclear pore complex
10.1038/S41422-022-00632-Y
ISSN:1001-0602
Extended DNA threading through a dual-engine motor module of the activating signal co-integrator 1 complex
Jia Junqiao•Hilal Tarek•Bohnsack Katherine E.•Chernev Aleksandar•Tsao Ning等 14 人
Nature Communications
2023
•2023/4/5
•Vol.14 No.1 p.1-14
Activating signal co-integrator 1 complex (ASCC) subunit 3 (ASCC3) supports diverse genome maintenance and gene expression processes, and contains tandem Ski2-like NTPase/helicase cassettes crucial for these functions. Presently, the molecular mechanisms underlying ASCC3 helicase activity and regula...
Cryoelectron microscopyDNADNA repair enzymesEnzyme mechanisms
10.1038/S41467-023-37528-3
ISSN:2041-1723
RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site
Katarzyna Z. Haza•Heather L. Martin•Ajinkya Rao•Amy L. Turner•Sophie E. Saunders等 21 人
Nature Communications
2021
•2021/6/30
•Vol.12 No.1 p.1-15
RAS mutations are the most common oncogenic drivers across human cancers, but there remains a paucity of clinically-validated pharmacological inhibitors of RAS, as druggable pockets have proven difficult to identify. Here, we identify two RAS-binding Affimer proteins, K3 and K6, that inhibit nucleot...
Cancer therapyOncogenesRecombinant protein therapyX-ray crystallography
10.1038/S41467-021-24316-0
ISSN:2041-1723
Phospholipid translocation captured in a bifunctional membrane protein MprF
Danfeng Song•Haizhan Jiao•Zhenfeng Liu
Nature Communications
2021
•2021/5/18
•Vol.12 No.1 p.1-16
As a large family of membrane proteins crucial for bacterial physiology and virulence, the Multiple Peptide Resistance Factors (MprFs) utilize two separate domains to synthesize and translocate aminoacyl phospholipids to the outer leaflets of bacterial membranes. The function of MprFs enables Staphy...
Bacterial structural biologyCryoelectron microscopyStructural biology
10.1038/S41467-021-23248-Z
ISSN:2041-1723
The evolution of multiple active site configurations in a designed enzyme
Nan-Sook Hong•Dušan Petrović•Richmond Lee•Ganna Gryn’ova•Miha Purg等 16 人
Nature Communications
2018
•2018/9/25
•Vol.9 No.1 p.1-10
Developments in computational chemistry, bioinformatics, and laboratory evolution have facilitated the de novo design and catalytic optimization of enzymes. Besides creating useful catalysts, the generation and iterative improvement of designed enzymes can provide valuable insight into the interplay...
Computational modelsSynthetic chemistry methodologyMolecular conformation
10.1038/S41467-018-06305-Y
ISSN:2041-1723
Molecular dynamics simulations elucidate the role of the F–F′ loop in substrate entry into CYP3A4
Junfang Yan•Hajime Hirao
Communications Chemistry
2026
•2026/1/9
•Vol.9 No.1 p.170
CYP3A4 metabolizes a significant proportion of all approved drugs in the human body. However, the mechanism by which substrates access the catalytic center in concert with conformational changes remains unresolved. Here, we captured spontaneous substrate-binding events from outside the enzyme to the...
Biophysical chemistryMolecular dynamics
10.1038/S42004-025-01815-5
ISSN:2399-3669
Predicting drug–protein interaction using quasi-visual question answering system
Shuangjia Zheng•Yongjian Li•Sheng Chen•Jun Xu•Yuedong Yang
Nature Machine Intelligence
2020
•2020/2/14
•Vol.2 No.2 p.134-140
Identifying novel drug–protein interactions is crucial for drug discovery. For this purpose, many machine learning-based methods have been developed based on drug descriptors and one-dimensional protein sequences. However, protein sequences cannot accurately reflect the interactions in three-dimensi...
Computational modelsMolecular medicineVirtual drug screening
10.1038/S42256-020-0152-Y
ISSN:2522-5839
Cryo-EM and directed evolution reveal how Arabidopsis nitrilase specificity is influenced by its quaternary structure
Andani E. Mulelu•Angela M. Kirykowicz•Jeremy D. Woodward
Communications Biology
2019
•2019/7/17
•Vol.2 No.1 p.1-11
Nitrilases are helical enzymes that convert nitriles to acids and/or amides. All plants have a nitrilase 4 homolog specific for ß-cyanoalanine, while in some plants neofunctionalization has produced nitrilases with altered specificity. Plant nitrilase substrate size and specificity correlate with he...
BiocatalysisElectron microscopyHydrolasesProtein designSecondary metabolism
10.1038/S42003-019-0505-4
ISSN:2399-3642
Structural basis for metal ion transport by the human SLC11 proteins DMT1 and NRAMP1
Márton Liziczai•Ariane Fuchs•Cristina Manatschal•Raimund Dutzler
Nature Communications
2025
•2025/1/17
•Vol.16 No.1 p.1-16
Iron and manganese are essential nutrients whose transport across membranes is catalyzed by members of the SLC11 family. In humans, this protein family contains two paralogs, the ubiquitously expressed DMT1, which is involved in the uptake and distribution of Fe2+ and Mn2+, and NRAMP1, which partici...
Cryoelectron microscopyIon transportIronPermeation and transport
10.1038/S41467-024-54705-0
ISSN:2041-1723
Deciphering RNA–ligand binding specificity with GerNA-Bind
Yunpeng Xia•Jiayi Li•Yi-Ting Chu•Jiahua Rao•Jing Chen等 9 人
Nature Machine Intelligence
2025
•2025/12/12
•00 p.1-13
RNA molecules are essential regulators of biological processes and promising therapeutic targets for various diseases. Discovering small molecules that selectively bind to specific RNA conformations remains challenging due to RNA’s structural complexity and the limited availability of high-resolutio...
Drug discoveryMachine learningRNA
10.1038/S42256-025-01154-Z
ISSN:2522-5839
Mining antibody functionality via AI-guided structural landscape profiling
Stanislav S. Terekhov•Nikita V. Ivanisenko•Nan Zhang•Yuliana A. Mokrushina•Dmitry E. Nolde等 35 人
Nature Communications
2026
•2026/3/15
0Despite substantial progress in single-cell screening techniques, antibody (Ab) repertoires still remain enigmatic. Here we show that Ab sequences can be linked to their functionality by using big data obtained from high-throughput sequencing. Using the expansive SARS-CoV-2 pandemic data, we develop...
AntibodiesInfectionMolecular modellingProtein function predictionsX-ray crystallography
10.1038/S41467-026-70553-6
ISSN:2041-1723
Cryo-EM structures of human organic anion transporting polypeptide OATP1B1
Ziyang Shan•Xuemei Yang•Huihui Liu•Yafei Yuan•Yuan Xiao等 11 人
Cell Research
2023
•2023/9/6
•00 p.1-12
Members of the solute carrier organic anion transporting polypeptide (OATPs) family function as transporters for a large variety of amphipathic organic anions including endogenous metabolites and clinical drugs, such as bile salts, steroids, thyroid hormones, statins, antibiotics, antivirals, and an...
Cryoelectron microscopyTransport carrier
10.1038/S41422-023-00870-8
ISSN:1748-7838
BRD9 degraders as chemosensitizers in acute leukemia and multiple myeloma
Weisberg Ellen•Chowdhury Basudev•Meng Chengcheng•Case Abigail E.•Ni Wei等 33 人
Blood Cancer Journal
2022
•2022/7/19
•Vol.12 No.7 p.1-10
Bromodomain-containing protein 9 (BRD9), an essential component of the SWI/SNF chromatin remodeling complex termed ncBAF, has been established as a therapeutic target in a subset of sarcomas and leukemias. Here, we used novel small molecule inhibitors and degraders along with RNA interference to ass...
CancerTargeted therapies
10.1038/S41408-022-00704-7
ISSN:2044-5385
Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance
Shaqra Ala M.•Zvornicanin Sarah N.•Huang Qiu Yu J.•Lockbaum Gordon J.•Knapp Mark等 13 人
Nature Communications
2022
•2022/6/21
•Vol.13 No.1 p.1-11
Coronaviruses can evolve and spread rapidly to cause severe disease morbidity and mortality, as exemplified by SARS-CoV-2 variants of the COVID-19 pandemic. Although currently available vaccines remain mostly effective against SARS-CoV-2 variants, additional treatment strategies are needed. Inhibito...
ProteasesViral infectionViral proteinsX-ray crystallography
10.1038/S41467-022-31210-W
ISSN:2041-1723
Assisting and accelerating NMR assignment with restrained structure prediction
Sirui Liu•Haotian Chu•Yuhao Xie•Fangming Wu•Fangjing Mu等 17 人
Communications Biology
2025
•2025/7/18
•Vol.8 No.1 p.1-10
Accurate dynamic protein structures are essential for drug design. NMR experiments can detect protein structures and potential dynamics, but the spectrum assignment and structure determination requires expertise and is time-consuming, while deep-learning-based structure predictions may be inconsiste...
BioinformaticsMachine learningProtein structure predictionsSolution-state NMR
10.1038/S42003-025-08466-1
ISSN:2399-3642
A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes
Yu Guo•Lisu Huang•Guangshun Zhang•Yanfeng Yao•He Zhou等 48 人
Nature Communications
2021
•2021/5/11
•Vol.12 No.1 p.1-11
COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies ...
Antibody therapySARS-CoV-2X-ray crystallography
10.1038/S41467-021-22926-2
ISSN:2041-1723
FOXI3 pathogenic variants cause one form of craniofacial microsomia
Mao Ke•Borel Christelle•Ansar Muhammad•Jolly Angad•Makrythanasis Periklis等 54 人
Nature Communications
2023
•2023/4/11
•Vol.14 No.1 p.1-16
Craniofacial microsomia (CFM; also known as Goldenhar syndrome), is a craniofacial developmental disorder of variable expressivity and severity with a recognizable set of abnormalities. These birth defects are associated with structures derived from the first and second pharyngeal arches, can occur ...
DevelopmentGeneticsMolecular medicine
10.1038/S41467-023-37703-6
ISSN:2041-1723
The interaction of DNA repair factors ASCC2 and ASCC3 is affected by somatic cancer mutations
Junqiao Jia•Eva Absmeier•Nicole Holton•Agnieszka J. Pietrzyk-Brzezinska•Philipp Hackert等 8 人
Nature Communications
2020
•2020/11/2
•Vol.11 No.1 p.1-13
The ASCC3 subunit of the activating signal co-integrator complex is a dual-cassette Ski2-like nucleic acid helicase that provides single-stranded DNA for alkylation damage repair by the α-ketoglutarate-dependent dioxygenase AlkBH3. Other ASCC components integrate ASCC3/AlkBH3 into a complex DNA repa...
DNAX-ray crystallography
10.1038/S41467-020-19221-X
ISSN:2041-1723
KDM3B inhibitors disrupt the oncogenic activity of PAX3-FOXO1 in fusion-positive rhabdomyosarcoma
Yong Yean Kim•Berkley E. Gryder•Ranuka Sinniah•Megan L. Peach•Jack F. Shern等 32 人
Nature Communications
2024
•2024/2/24
•Vol.15 No.1 p.1-19
Fusion-positive rhabdomyosarcoma (FP-RMS) is an aggressive pediatric sarcoma driven primarily by the PAX3-FOXO1 fusion oncogene, for which therapies targeting PAX3-FOXO1 are lacking. Here, we screen 62,643 compounds using an engineered cell line that monitors PAX3-FOXO1 transcriptional activity iden...
Cancer epigeneticsDrug developmentSarcoma
10.1038/S41467-024-45902-Y
ISSN:2041-1723
Integrated structure prediction of protein–protein docking with experimental restraints using ColabDock
Shihao Feng•Zhenyu Chen•Chengwei Zhang•Yuhao Xie•Sergey Ovchinnikov等 7 人
Nature Machine Intelligence
2024
•2024/8/5
•00 p.1-12
Protein complex structure prediction plays important roles in various applications, such as drug discovery and antibody design. However, due to limited prediction accuracy, there are frequent inconsistencies between the predictions and the experiments. Here we present ColabDock, a general framework ...
Machine learningMolecular modellingProtein structure predictionsSoftware
10.1038/S42256-024-00873-Z
ISSN:2522-5839
Structure of an MHC I–tapasin–ERp57 editing complex defines chaperone promiscuity
Müller Ines Katharina•Winter Christian•Thomas Christoph•Spaapen Robbert M.•Trowitzsch Simon等 6 人
Nature Communications
2022
•2022/9/14
•Vol.13 No.1 p.1-10
Adaptive immunity depends on cell surface presentation of antigenic peptides by major histocompatibility complex class I (MHC I) molecules and on stringent ER quality control in the secretory pathway. The chaperone tapasin in conjunction with the oxidoreductase ERp57 is crucial for MHC I assembly an...
Membrane structure and assemblyMHC class IX-ray crystallography
10.1038/S41467-022-32841-9
ISSN:2041-1723
Structural insight into the substrate recognition and transport mechanism of the human LAT2–4F2hc complex
Renhong Yan•Jiayao Zhou•Yaning Li•Jianlin Lei•Qiang Zhou
Cell Discovery
2020
•2020/11/10
•Vol.6 No.1 p.1-4
Cell biologyStructural biology
10.1038/S41421-020-00207-4
ISSN:2056-5968
Structural basis of sex pheromone detection in aphids
Zhi Dong•Yidong Wang•Ying Tian•Zeyuan Guan•Minghui Bai等 15 人
Cell Research
2026
•2026/6/22
•00 p.1-13
Sex pheromones play a central role in regulating animal behavior and reproduction. In insects, these signals are perceived through specialized odorant receptors (ORs) that mediate species-specific communication and safeguard genetic integrity. However, the structural basis of sex pheromone detection...
Cryoelectron microscopyIon channel signalling
10.1038/S41422-026-01267-Z
ISSN:1748-7838
Structural and immunological characterization of the H3 influenza hemagglutinin during antigenic drift
Rebeca de Paiva Froes Rocha•Ilhan Tomris•Charles A. Bowman•Emma Stevens•Jason Kantorow等 19 人
Nature Communications
2025
•2025/12/11
0The quest for a universal influenza vaccine holds great promise for mitigating the global burden of influenza-related morbidity and mortality. However, challenges persist in identifying conserved epitopes capable of eliciting robust and durable immune responses. In this study, we explore the influen...
Cryoelectron microscopyInfluenza virus
10.1038/S41467-025-66375-7
ISSN:2041-1723
Mechanism of an intramembrane chaperone for multipass membrane proteins
Smalinskaitė Luka•Kim Min Kyung•Lewis Aaron J. O.•Keenan Robert J.•Hegde Ramanujan S.
Nature
2022
•2022/10/19
•Vol.611 No.7934 p.161-166
Multipass membrane proteins play numerous roles in biology and include receptors, transporters, ion channels and enzymes1,2. How multipass proteins are co-translationally inserted and folded at the endoplasmic reticulum is not well understood2. The prevailing model posits that each transmembrane dom...
ChaperonesCryoelectron microscopyEndoplasmic reticulum
10.1038/S41586-022-05336-2
ISSN:0028-0836
Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP(1,2) in a position elevated from the virion membrane
Kathryn M. Hastie•Zhe Li Salie•Zunlong Ke•Peter J. Halfmann•Lisa Evans DeWald等 26 人
Nature Communications
2025
•2025/2/3
•Vol.16 No.1 p.1-12
Monoclonal antibodies (mAbs) against Ebola virus (EBOV) glycoprotein (GP1,2) are the standard of care for Ebola virus disease (EVD). Anti-GP1,2 mAbs targeting the stalk and membrane proximal external region (MPER) potently neutralize EBOV in vitro and are protective in a mouse model of EVD. However,...
ImmunologyStructural biologyVirology
10.1038/S41467-025-56452-2
ISSN:2041-1723
INI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication
Updesh Dixit•Savita Bhutoria•Xuhong Wu•Liming Qiu•Menachem Spira等 20 人
Nature Communications
2021
•2021/5/12
•Vol.12 No.1 p.1-15
INI1/SMARCB1 binds to HIV-1 integrase (IN) through its Rpt1 domain and exhibits multifaceted role in HIV-1 replication. Determining the NMR structure of INI1-Rpt1 and modeling its interaction with the IN-C-terminal domain (IN-CTD) reveal that INI1-Rpt1/IN-CTD interface residues overlap with those re...
NMR spectroscopyRetrovirusVirus–host interactions
10.1038/S41467-021-22733-9
ISSN:2041-1723
Sliding-attention transformer neural architecture for predicting T cell receptor–antigen–human leucocyte antigen binding
Ziyan Feng•Jingyang Chen•Youlong Hai•Xuelian Pang•Kun Zheng等 16 人
Nature Machine Intelligence
2024
•2024/9/27
•00 p.1-15
Neoantigens are promising targets for immunotherapy by eliciting immune response and removing cancer cells with high specificity, low toxicity and ease of personalization. However, identifying effective neoantigens remains difficult because of the complex interactions among T cell receptors, antigen...
Computational biology and bioinformaticsImmunology
10.1038/S42256-024-00901-Y
ISSN:2522-5839
The ribosome lowers the entropic penalty of protein folding
Julian O. Streit•Ivana V. Bukvin•Sammy H. S. Chan•Shahzad Bashir•Lauren F. Woodburn等 14 人
Nature
2024
•2024/8/7
•00 p.1-8
Most proteins fold during biosynthesis on the ribosome1, and co-translational folding energetics, pathways and outcomes of many proteins have been found to differ considerably from those in refolding studies2–10. The origin of this folding modulation by the ribosome has remained unknown. Here we hav...
Solution-state NMRThermodynamics
10.1038/S41586-024-07784-4
ISSN:0028-0836
TRPC channels blockade abolishes endotoxemic cardiac dysfunction by hampering intracellular inflammation and Ca2+ leakage
Tang Na•Tian Wen•Ma Guang-Yuan•Xiao Xiong•Zhou Lei等 20 人
Nature Communications
2022
•2022/12/2
•Vol.13 No.1 p.1-21
Intracellular Ca2+ dysregulation is a key marker in septic cardiac dysfunction; however, regulation of the classic Ca2+ regulatory modules cannot successfully abolish this symptom. Here we show that the knockout of transient receptor potential canonical (TRPC) channel isoforms TRPC1 and TRPC6 can am...
CardiomyopathiesDrug development
10.1038/S41467-022-35242-0
ISSN:2041-1723
High-resolution crystal structure of arthropod Eiger TNF suggests a mode of receptor engagement and altered surface charge within endosomes
Mattia Bertinelli•Guido C. Paesen•Jonathan M. Grimes•Max Renner
Communications Biology
2019
•2019/8/6
•Vol.2 No.1 p.1-10
The tumour necrosis factor alpha (TNFα) superfamily of proteins are critical in numerous biological processes, such as in development and immunity. Eiger is the sole TNFα member described in arthropods such as in the important model organism Drosophila. To date there are no structural data on any Ei...
ApoptosisCell signallingX-ray crystallography
10.1038/S42003-019-0541-0
ISSN:2399-3642
Control of CD1d-restricted antigen presentation and inflammation by sphingomyelin
Espen Melum•Xiaojun Jiang•Kristi D. Baker•M. Fatima Macedo•Jürgen Fritsch等 21 人
Nature Immunology
2019
•2019/10/21
•Vol.20 No.12 p.1644-1655
Invariant natural killer T (iNKT) cells recognize activating self and microbial lipids presented by CD1d. CD1d can also bind non-activating lipids, such as sphingomyelin. We hypothesized that these serve as endogenous regulators and investigated humans and mice deficient in acid sphingomyelinase (AS...
ImmunologyInflammation
10.1038/S41590-019-0504-0
ISSN:1529-2908
2.7 Å cryo-EM structure of ex vivo RML prion fibrils
Manka Szymon W.•Zhang Wenjuan•Wenborn Adam•Betts Jemma•Joiner Susan等 8 人
Nature Communications
2022
•2022/7/13
•Vol.13 No.1 p.1-11
Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion...
Cryoelectron microscopyPrionsProtein aggregation
10.1038/S41467-022-30457-7
ISSN:2041-1723
The crystal structure of a simian Foamy Virus receptor binding domain provides clues about entry into host cells
Fernández Ignacio•Dynesen Lasse Toftdal•Coquin Youna•Pederzoli Riccardo•Brun Delphine等 10 人
Nature Communications
2023
•2023/3/6
•Vol.14 No.1 p.1-14
The surface envelope glycoprotein (Env) of all retroviruses mediates virus binding to cells and fusion of the viral and cellular membranes. A structure-function relationship for the HIV Env that belongs to the Orthoretrovirus subfamily has been well established. Structural information is however lar...
RetrovirusVirus–host interactionsX-ray crystallography
10.1038/S41467-023-36923-0
ISSN:2041-1723
Biosynthesis of peptide–nucleobase hybrids in ribosomal peptides
Zeng-Fei Pei•Natalia M. Vior•Lingyang Zhu•Andrew W. Truman•Satish K. Nair
Nature Chemical Biology
2024
•2024/9/16
•00 p.1-12
The main biopolymers in nature are oligonucleotides and polypeptides. However, naturally occurring peptide–nucleobase hybrids are rare. Here we report the characterization of the founding member of a class of peptide–nucleobase hybrid natural products with a pyrimidone motif from a widely distribute...
BiosynthesisEnzymesPeptides
10.1038/S41589-024-01736-9
ISSN:1552-4450
Structure of the class D GPCR Ste2 dimer coupled to two G proteins
Vaithish Velazhahan•Ning Ma•Gáspár Pándy-Szekeres•Albert J. Kooistra•Yang Lee等 8 人
Nature
2020
•2020/12/2
•Vol.589 No.7840 p.148-153
G-protein-coupled receptors (GPCRs) are divided phylogenetically into six classes1,2, denoted A to F. More than 370 structures of vertebrate GPCRs (belonging to classes A, B, C and F) have been determined, leading to a substantial understanding of their function3. By contrast, there are no structure...
Cryoelectron microscopyFungal biology
10.1038/S41586-020-2994-1
ISSN:0028-0836
OpenFold: retraining AlphaFold2 yields new insights into its learning mechanisms and capacity for generalization
Gustaf Ahdritz•Nazim Bouatta•Christina Floristean•Sachin Kadyan•Qinghui Xia等 34 人
Nature Methods
2024
•2024/5/14
•00 p.1-11
AlphaFold2 revolutionized structural biology with the ability to predict protein structures with exceptionally high accuracy. Its implementation, however, lacks the code and data required to train new models. These are necessary to (1) tackle new tasks, like protein–ligand complex structure predicti...
Machine learningProtein folding
10.1038/S41592-024-02272-Z
ISSN:1548-7091
Assessing and engineering the IscB–ωRNA system for programmed genome editing
Hao Yan•Xiaoqing Tan•Siyuan Zou•Yihong Sun•Ailong Ke等 6 人
Nature Chemical Biology
2024
•2024/7/8
•00 p.1-12
OMEGA RNA (ωRNA)-guided endonuclease IscB, the evolutionary ancestor of Cas9, is an attractive system for in vivo genome editing because of its compact size and mechanistic resemblance to Cas9. However, wild-type IscB–ωRNA systems show limited activity in human cells. Here we report enhanced OgeuIsc...
EnzymesSystems biology
10.1038/S41589-024-01669-3
ISSN:1552-4450
Structural basis for E4 enzyme Ufd2-catalyzed K48/K29 branched ubiquitin chains
Zebin Tong•Xiangwei Wu•Hongyi Cai•Shidian Wu•Tianyi Zhang等 11 人
Nature Chemical Biology
2025
•2025/8/15
•00 p.1-10
E4 enzymes amplify and remodel ubiquitin chain signals beyond the conventional E1–E2–E3 cascade. The first identified E4 enzyme Ufd2 preferentially catalyzes K48/K29 branched ubiquitin chains, yet the structural mechanism remains unknown. Here, we combined chemical biology and cryo-electron microsco...
Chemical modificationEnzyme mechanismsPost-translational modifications
10.1038/S41589-025-01985-2
ISSN:1552-4450
Human PLD structures enable drug design and characterization of isoenzyme selectivity
Claire M. Metrick•Emily A. Peterson•Joseph C. Santoro•Istvan J. Enyedy•Paramasivam Murugan等 12 人
Nature Chemical Biology
2020
•2020/2/10
•Vol.16 No.4 p.391-399
Phospholipase D enzymes (PLDs) are ubiquitous phosphodiesterases that produce phosphatidic acid (PA), a key second messenger and biosynthetic building block. Although an orthologous bacterial Streptomyces sp. strain PMF PLD structure was solved two decades ago, the molecular basis underlying the fun...
BiochemistryEnzyme mechanismsEnzymesLipidsStructural biology
10.1038/S41589-019-0458-4
ISSN:1552-4450
Molecular basis of foreign DNA recognition by BREX anti-phage immunity system
Alena Drobiazko•Myfanwy C. Adams•Mikhail Skutel•Kristina Potekhina•Oksana Kotovskaya等 13 人
Nature Communications
2025
•2025/2/20
•Vol.16 No.1 p.1-21
Anti-phage systems of the BREX (BacteRiophage EXclusion) superfamily rely on site-specific epigenetic DNA methylation to discriminate between the host and invading DNA. We demonstrate that in Type I BREX systems, defense and methylation require BREX site DNA binding by the BrxX (PglX) methyltransfer...
BacteriophagesCryoelectron microscopyDNA metabolismDNA restriction-modification enzymes
10.1038/S41467-025-57006-2
ISSN:2041-1723
Structural basis for genome-wide site-specific DNA recognition by Nuclear Factor IA
Ci Zhu•Ding Xiao•Zhipu Luo•Jie Zhang•Shuang Liu等 13 人
Nature Communications
2025
•2025/12/15
0Nuclear Factor IA, a member of the long-studied Nuclear Factor I family of DNA-binding proteins, plays pivotal roles in development and metabolism. Dysregulation or loss of Nuclear Factor IA is associated with severe neurological defects in humans and disruptions in fatty acid metabolism linked to c...
SAXSTranscriptional regulatory elementsX-ray crystallography
10.1038/S41467-025-67641-4
ISSN:2041-1723
Explicit description of viral capsid subunit shapes by unfolding dihedrons
Ryuya Toyooka•Seri Nishimoto•Tomoya Tendo•Takashi Horiyama•Tomohiro Tachi等 6 人
Communications Biology
2024
•2024/11/14
•Vol.7 No.1 p.1-9
Viral capsid assembly and the design of capsid-based nanocontainers critically depend on understanding the shapes and interfaces of constituent protein subunits. However, a comprehensive framework for characterizing these features is still lacking. Here, we introduce a novel approach based on spheri...
Computational biophysicsMolecular modellingSupramolecular assembly
10.1038/S42003-024-07218-X
ISSN:2399-3642
Integrated experimental and AI innovations for RNA structure determination
Wenkai Wang•Baoquan Su•Zhenling Peng•Jianyi Yang
Nature Biotechnology
2026
•2026/1/5
•Vol.44 No.2 p.205-214
RNAs act as crucial ‘social’ mediators within the cell, orchestrating a wide array of biological processes. Their functionality hinges on their complex three-dimensional structures, which dictate stability, binding specificity and molecular interactions. In recent years, a surge of research has focu...
Computational modelsStructural biologyStructure determination
10.1038/S41587-025-02974-5
ISSN:1087-0156
Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice
Lin Wang•Dominik Aschenbrenner•Zhiyang Zeng•Xiya Cao•Daniel Mayr等 55 人
Nature Genetics
2021
•2021/3/29
•00 p.1-11
Spleen tyrosine kinase (SYK) is a critical immune signaling molecule and therapeutic target. We identified damaging monoallelic SYK variants in six patients with immune deficiency, multi-organ inflammatory disease such as colitis, arthritis and dermatitis, and diffuse large B cell lymphomas. The SYK...
Severe combined immunodeficiencyUlcerative colitis
10.1038/S41588-021-00803-4
ISSN:1061-4036
Inhibition of M. tuberculosis and human ATP synthase by BDQ and TBAJ-587
Yuying Zhang•Yuezheng Lai•Shan Zhou•Ting Ran•Yue Zhang等 19 人
Nature
2024
•2024/7/3
•Vol.631 No.8020 p.409-414
Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium tuberculosis by inhibiting ATP synthase1,2. However, BDQ also inhibits human ATP synthase3. At present, how these compounds interact with eith...
Drug safetySmall molecules
10.1038/S41586-024-07605-8
ISSN:0028-0836
Structural analysis of full-length human transmembrane protein 94 argues against its classification as a P-type Mg2+ ATPase
Yuqi Li•Ye Cong•Xinyao Lou•Weiping Li•Runhao Wang等 10 人
Cell Discovery
2025
•2025/6/3
•Vol.11 No.1 p.540
Cryoelectron microscopyEndoplasmic reticulum
10.1038/S41421-025-00806-Z
ISSN:2056-5968
Bidirectional communication between nucleotide and substrate binding sites in a type IV multidrug ABC transporter
Victor Hugo Pérez Carrillo•Margot Di Cesare•Dania Rose-Sperling•Waqas Javed•Hannes Neuweiler等 9 人
Nature Communications
2025
•2025/11/11
•Vol.16 No.1 p.99210
ATP-binding cassette (ABC) transporters use ATP to transport substrates across membranes. In type IV ABC transporters, which include many multidrug resistance (MDR) pumps, communication between nucleotide-binding domains (NBDs) and transmembrane domains (TMDs) is mediated via large intracellular dom...
Mass spectrometryMembrane proteinsSolution-state NMR
10.1038/S41467-025-65037-Y
ISSN:2041-1723
Biofunctionalized dissolvable hydrogel microbeads enable efficient characterization of native protein complexes
Xinyang Shao•Meng Tian•Junlong Yin•Haifeng Duan•Ye Tian等 16 人
Nature Communications
2024
•2024/10/5
•Vol.15 No.1 p.1-18
The characterization of protein complex is vital for unraveling biological mechanisms in various life processes. Despite advancements in biophysical tools, the capture of non-covalent complexes and deciphering of their biochemical composition continue to present challenges for low-input samples. Her...
Biophysical methodsMass spectrometryProtein enrichmentStructural biology
10.1038/S41467-024-52948-5
ISSN:2041-1723
Early intermediates in bacterial RNA polymerase promoter melting visualized by time-resolved cryo-electron microscopy
Ruth M. Saecker•Andreas U. Mueller•Brandon Malone•James Chen•William C. Budell等 14 人
Nature Structural & Molecular Biology
2024
•2024/7/1
•00 p.1-11
During formation of the transcription-competent open complex (RPo) by bacterial RNA polymerases (RNAPs), transient intermediates pile up before overcoming a rate-limiting step. Structural descriptions of these interconversions in real time are unavailable. To address this gap, here we use time-resol...
Cryoelectron microscopyTranscription
10.1038/S41594-024-01349-9
ISSN:1545-9993
Structural basis for antibody recognition of vulnerable epitopes on Nipah virus F protein
Byrne Patrick O.•Fisher Brian E.•Ambrozak David R.•Blade Elizabeth G.•Tsybovsky Yaroslav等 8 人
Nature Communications
2023
•2023/3/17
•Vol.14 No.1 p.1-12
Nipah virus (NiV) is a pathogenic paramyxovirus that causes fatal encephalitis in humans. Two envelope glycoproteins, the attachment protein (G/RBP) and fusion protein (F), facilitate entry into host cells. Due to its vital role, NiV F presents an attractive target for developing vaccines and therap...
Cryoelectron microscopyInfectious diseasesVirology
10.1038/S41467-023-36995-Y
ISSN:2041-1723
Crystal structures of human ET B receptor provide mechanistic insight into receptor activation and partial activation
Wataru Shihoya•Tamaki Izume•Asuka Inoue•Keitaro Yamashita•Francois Marie Ngako Kadji等 9 人
Nature Communications
2018
•2018/11/9
•Vol.9 No.1 p.1-11
Endothelin receptors (ETA and ETB) are class A GPCRs activated by vasoactive peptide endothelins, and are involved in blood pressure regulation. ETB-selective signalling induces vasorelaxation, and thus selective ETB agonists are expected to be utilized for improved anti-tumour drug delivery and neu...
Hormone receptorsX-ray crystallography
10.1038/S41467-018-07094-0
ISSN:2041-1723
Cryo-EM structure of the respiratory I + III2 supercomplex from Arabidopsis thaliana at 2 Å resolution
Klusch Niklas•Dreimann Maximilian•Senkler Jennifer•Rugen Nils•Kühlbrandt Werner等 6 人
Nature Plants
2022
•2022/12/30
•Vol.9 No.1 p.142-156
Protein complexes of the mitochondrial respiratory chain assemble into respiratory supercomplexes. Here we present the high-resolution electron cryo-microscopy structure of the Arabidopsis respiratory supercomplex consisting of complex I and a complex III dimer, with a total of 68 protein subunits a...
Cryoelectron microscopyPlant molecular biology
10.1038/S41477-022-01308-6
ISSN:2055-0278
Molecular mechanism of PINK1 regulation by the Hsp90 machinery
Xuyang Tian•Jiayue Su•Ziyi Wang•Tao Liu•Huifang Xiong等 8 人
Nature Communications
2025
•2025/12/1
•Vol.16 No.1 p.108010
Hundreds of human kinases, including PINK1—a protein kinase associated with familial Parkinson’s disease—are regulated by Hsp90 and its cochaperones. While previous studies have elucidated the mechanism of kinase loading into the Hsp90 machinery, the subsequent regulation of kinases by Hsp90 and its...
ChaperonesCryoelectron microscopyKinases
10.1038/S41467-025-65859-W
ISSN:2041-1723
Predicting unseen antibodies’ neutralizability via adaptive graph neural networks
Zhang Jie•Du Yishan•Zhou Pengfei•Ding Jinru•Xia Shuai等 13 人
Nature Machine Intelligence
2022
•2022/11/7
•Vol.4 No.11 p.964-976
Most natural and synthetic antibodies are ‘unseen’. That is, the demonstration of their neutralization effects with any antigen requires laborious and costly wet-lab experiments. The existing methods that learn antibody representations from known antibody–antigen interactions are unsuitable for unse...
ImmunologyMathematics and computingSARS-CoV-2
10.1038/S42256-022-00553-W
ISSN:2522-5839
Cryo-EM structures of Nipah virus polymerases and high-throughput RdRp assay development enable anti-NiV drug discovery
Zhenhang Chen•Jeanne Quirit Dudley•Colin Deniston•Cosmo Z. Buffalo•Debjani Patra等 18 人
Nature Communications
2025
•2025/7/19
•Vol.16 No.1 p.1-14
Transcription and replication of the Nipah virus (NiV) are driven by the large protein (L) together with its essential co-factor phosphoprotein (P). L encodes all the viral enzymatic functions, including RNA-dependent RNA polymerase (RdRp) activity, while the tetrameric P is multi-modular. Here, we ...
Cryoelectron microscopyEnzyme mechanismsVirology
10.1038/S41467-025-61764-4
ISSN:2041-1723
Structural bases for Na+-Cl− cotransporter inhibition by thiazide diuretic drugs and activation by kinases
Yongxiang Zhao•Heidi Schubert•Alan Blakely•Biff Forbush•Micholas Dean Smith等 7 人
Nature Communications
2024
•2024/8/14
•Vol.15 No.1 p.1-13
The Na+-Cl− cotransporter (NCC) drives salt reabsorption in the kidney and plays a decisive role in balancing electrolytes and blood pressure. Thiazide and thiazide-like diuretics inhibit NCC-mediated renal salt retention and have been cornerstones for treating hypertension and edema since the 1950s...
BiophysicsElectron microscopyIon channels
10.1038/S41467-024-51381-Y
ISSN:2041-1723
Structural basis for human chondroitin sulfate chain polymerization
Poushalee Dutta•Rosa L. Cordeiro•Mélanie Friedel-Arboleas•Marie Bourgeais•Sylvain D. Vallet等 12 人
Nature Communications
2025
•2025/11/26
0Chondroitin sulfates are complex polysaccharide chains that regulate various biological processes at the cell surface and within the extracellular matrix. Here, we identify four heterodimeric complexes responsible for chondroitin sulfate chain polymerization in humans: CHSY1-CHPF, CHSY1-CHPF2, CHSY3...
Cryoelectron microscopyEnzyme mechanismsGlycobiologyGlycosylation
10.1038/S41467-025-66787-5
ISSN:2041-1723
A formally exact method for high-throughput absolute binding-free-energy calculations
Hengwei Bian•Xueguang Shao•Christophe Chipot•Wensheng Cai•Haohao Fu
Nature Computational Science
2025
•2025/6/18
•00 p.1-6
Here we introduce a high-throughput, formally exact method for absolute binding-free-energy calculations that enhances computational efficiency and accuracy. At the core of this method is a thermodynamic cycle that minimizes protein ligand relative motion, thereby reducing system perturbations and d...
High-throughput screeningMolecular dynamicsVirtual drug screening
10.1038/S43588-025-00821-W
ISSN:2662-8457
Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines
Lee Sherry•Mohammad W. Bahar•Claudine Porta•Helen Fox•Keith Grehan等 23 人
Nature Communications
2025
•2025/1/18
•Vol.16 No.1 p.1-17
Polioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines in the mid-1900’s, which dramatically reduced disease prevalence. Continued use of these vaccines, however, threatens ultimate disease eradication and achievement of a polio-free world...
Protein vaccinesVirus structures
10.1038/S41467-025-56118-Z
ISSN:2041-1723
Molecular mechanism of phosphopeptide neoantigen immunogenicity
Yury Patskovsky•Aswin Natarajan•Larysa Patskovska•Samantha Nyovanie•Bishnu Joshi等 18 人
Nature Communications
2023
•2023/6/23
•Vol.14 No.1 p.1-18
Altered protein phosphorylation in cancer cells often leads to surface presentation of phosphopeptide neoantigens. However, their role in cancer immunogenicity remains unclear. Here we describe a mechanism by which an HLA-B*0702-specific acute myeloid leukemia phosphoneoantigen, pMLL747–755 (EPR(pS)...
MHCMolecular modellingSolution-state NMRTumour immunologyX-ray crystallography
10.1038/S41467-023-39425-1
ISSN:2041-1723
Extraction of protein dynamics information from cryo-EM maps using deep learning
Shigeyuki Matsumoto•Shoichi Ishida•Mitsugu Araki•Takayuki Kato•Kei Terayama等 6 人
Nature Machine Intelligence
2021
•2021/2/4
•Vol.3 No.2 p.153-160
Elucidation of both the three-dimensional structure and the dynamics of a protein is essential to understand its function. Technical breakthroughs in single-particle analysis based on cryo-electron microscopy (cryo-EM) have enabled the three-dimensional structures of numerous proteins to be solved a...
Computational biophysicsCryoelectron microscopyMachine learning
10.1038/S42256-020-00290-Y
ISSN:2522-5839
Structure of the native γ-tubulin ring complex capping spindle microtubules
Tom Dendooven•Stanislau Yatskevich•Alister Burt•Zhuo A. Chen•Dom Bellini等 8 人
Nature Structural & Molecular Biology
2024
•2024/4/12
•00 p.1-11
Microtubule (MT) filaments, composed of α/β-tubulin dimers, are fundamental to cellular architecture, function and organismal development. They are nucleated from MT organizing centers by the evolutionarily conserved γ-tubulin ring complex (γTuRC). However, the molecular mechanism of nucleation rema...
Chromosome segregationCryoelectron tomographyMitotic spindle
10.1038/S41594-024-01281-Y
ISSN:1545-9993
Structural basis for the recognition of HCoV-HKU1 by human TMPRSS2
Lingyun Xia•Yuanyuan Zhang•Qiang Zhou
Cell Research
2024
•2024/4/19
•00 p.1-4
Cryoelectron microscopyImmunology
10.1038/S41422-024-00958-9
ISSN:1748-7838
The main protease (Mpro) from SARS-CoV-2 triggers plasma clotting in vitro by activating coagulation factors VII and FXII
Anna Pagotto•Federico Uliana•Elena Cavedon•Giulia Nordio•Andrea Pierangelini等 15 人
Communications Biology
2025
•2025/8/1
•Vol.8 No.1 p.1-16
Although the connection between COVID-19 and coagulopathy has been clear since the beginning of SARS-CoV-2 pandemic, the underlying molecular mechanisms remain elusive. Available data support that the hyper-coagulant state is sustained by systemic inflammation. Here we show that the SARS-CoV-2 main ...
ProteasesSARS-CoV-2
10.1038/S42003-025-08570-2
ISSN:2399-3642
Total escape of SARS-CoV-2 from dual monoclonal antibody therapy in an immunocompromised patient
Jaki Lena•Weigang Sebastian•Kern Lisa•Kramme Stefanie•Wrobel Antoni G.等 24 人
Nature Communications
2023
•2023/4/10
•Vol.14 No.1 p.1-14
Monoclonal antibodies (mAbs) directed against the spike of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective therapeutic options to combat infections in high-risk patients. Here, we report the adaptation of SARS-CoV-2 to the mAb cocktail REGN-COV in a kidney transplant patie...
Immune evasionOutcomes researchSARS-CoV-2Viral evolutionViral infection
10.1038/S41467-023-37591-W
ISSN:2041-1723
Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants
Tomokazu Tamura•Jumpei Ito•Keiya Uriu•Jiri Zahradnik•Izumi Kida等 44 人
Nature Communications
2023
•2023/5/16
•Vol.14 No.1 p.1-20
In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer o...
SARS-CoV-2Viral evolutionVirus–host interactions
10.1038/S41467-023-38435-3
ISSN:2041-1723
Rational enzyme design for enabling biocatalytic Baldwin cyclization and asymmetric synthesis of chiral heterocycles
Li Jun-Kuan•Qu Ge•Li Xu•Tian Yuchen•Cui Chengsen等 10 人
Nature Communications
2022
•2022/12/19
•Vol.13 No.1 p.1-11
Chiral heterocyclic compounds are needed for important medicinal applications. We report an in silico strategy for the biocatalytic synthesis of chiral N- and O-heterocycles via Baldwin cyclization modes of hydroxy- and amino-substituted epoxides and oxetanes using the limonene epoxide hydrolase fro...
BiocatalysisEnzyme mechanismsHydrolasesSynthetic chemistry methodologyProtein design
10.1038/S41467-022-35468-Y
ISSN:2041-1723
A human monoclonal antibody binds within the poliovirus receptor-binding site to neutralize all three serotypes
Andrew J. Charnesky•Julia E. Faust•Hyunwook Lee•Rama Devudu Puligedda•Daniel J. Goetschius等 15 人
Nature Communications
2023
•2023/10/10
•Vol.14 No.1 p.1-11
Global eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines and antivirals. In support of this goal, we map the epitope of human monoclonal antibody 9H2 which is able to neutralize the three serotypes of poliovirus. Using cryo-EM we solve the near-atomic ...
Antiviral agentsCryoelectron microscopyVirus–host interactions
10.1038/S41467-023-41052-9
ISSN:2041-1723
Chlorophyll a / b binding-specificity in water-soluble chlorophyll protein
Daniel M. Palm•Alessandro Agostini•Vivien Averesch•Philipp Girr•Mara Werwie等 9 人
Nature Plants
2018
•2018/10/8
•Vol.4 No.11 p.920-929
We altered the chlorophyll (Chl) binding sites in various versions of water-soluble chlorophyll protein (WSCP) by amino acid exchanges to alter their preferences for either Chl a or Chl b. WSCP is ideally suited for this mutational analysis since it forms a tetrameric complex with only four identica...
Antenna complexBiochemical assaysBiophysical methodsPlant molecular biologyX-ray crystallography
10.1038/S41477-018-0273-Z
ISSN:2055-0278
Molecular mechanism and structural basis of small-molecule modulation of the gating of acid-sensing ion channel 1
Yi Liu•Jichun Ma•Renee L. DesJarlais•Rebecca Hagan•Jason Rech等 13 人
Communications Biology
2021
•2021/2/9
•Vol.4 No.1 p.1-15
Acid-sensing ion channels (ASICs) are proton-gated cation channels critical for neuronal functions. Studies of ASIC1, a major ASIC isoform and proton sensor, have identified acidic pocket, an extracellular region enriched in acidic residues, as a key participant in channel gating. While binding to t...
Ion transportX-ray crystallography
10.1038/S42003-021-01678-1
ISSN:2399-3642
Discovery of fungal oligosaccharide-oxidising flavo-enzymes with previously unknown substrates, redox-activity profiles and interplay with LPMOs
Majid Haddad Momeni•Folmer Fredslund•Bastien Bissaro•Olanrewaju Raji•Thu V. Vuong等 17 人
Nature Communications
2021
•2021/4/9
•Vol.12 No.1 p.1-13
Oxidative plant cell-wall processing enzymes are of great importance in biology and biotechnology. Yet, our insight into the functional interplay amongst such oxidative enzymes remains limited. Here, a phylogenetic analysis of the auxiliary activity 7 family (AA7), currently harbouring oligosacchari...
BiocatalysisFungiOxidoreductasesPolysaccharidesX-ray crystallography
10.1038/S41467-021-22372-0
ISSN:2041-1723
Polyphenol oxidases exhibit promiscuous proteolytic activity
A. Biundo•V. Braunschmid•M. Pretzler•I. Kampatsikas•B. Darnhofer等 9 人
Communications Chemistry
2020
•2020/5/15
•Vol.3 No.1 p.1-8
Tyrosinases catalyse both the cresolase and catecholase reactions for the formation of reactive compounds which are very important for industrial applications. In this study, we describe a proteolytic activity of tyrosinases. Two different tyrosinases originating from mushroom and apple are able to ...
BiocatalysisEnzyme mechanismsOxidoreductases
10.1038/S42004-020-0305-2
ISSN:2399-3669
MHC class II proteins mediate sialic acid independent entry of human and avian H2N2 influenza A viruses
Umut Karakus•Milagros Sempere Borau•Patricia Martínez-Barragán•Josephine von Kempis•Soner Yildiz等 12 人
Nature Microbiology
2024
•2024/7/15
•00 p.1-16
Influenza A viruses (IAV) pose substantial burden on human and animal health. Avian, swine and human IAV bind sialic acid on host glycans as receptor, whereas some bat IAV require MHC class II complexes for cell entry. It is unknown how this difference evolved and whether dual receptor specificity i...
Influenza virusVirus–host interactions
10.1038/S41564-024-01771-1
ISSN:2058-5276
Molecular mechanism of topoisomerase poisoning by the peptide antibiotic albicidin
Michalczyk Elizabeth•Hommernick Kay•Behroz Iraj•Kulike Marcel•Pakosz-Stępień Zuzanna等 16 人
Nature Catalysis
2023
•2023/1/23
•Vol.6 No.1 p.52-67
The peptide antibiotic albicidin is a DNA topoisomerase inhibitor with low-nanomolar bactericidal activity towards fluoroquinolone-resistant Gram-negative pathogens. However, its mode of action is poorly understood. We determined a 2.6 Å resolution cryoelectron microscopy structure of a ternary comp...
AntibioticsEnzyme mechanismsMechanism of actionStructure-based drug designTarget validation
10.1038/S41929-022-00904-1
ISSN:2520-1158
LTK mutations responsible for resistance to lorlatinib in non-small cell lung cancer harboring CLIP1-LTK fusion
Shunta Mori•Hiroki Izumi•Mitsugu Araki•Jie Liu•Yu Tanaka等 20 人
Communications Biology
2024
•2024/4/4
•Vol.7 No.1 p.1-10
The CLIP1-LTK fusion was recently discovered as a novel oncogenic driver in non-small cell lung cancer (NSCLC). Lorlatinib, a third-generation ALK inhibitor, exhibited a dramatic clinical response in a NSCLC patient harboring CLIP1-LTK fusion. However, it is expected that acquired resistance will in...
Non-small-cell lung cancerOncogenes
10.1038/S42003-024-06116-6
ISSN:2399-3642
Structures and mechanisms of tRNA methylation by METTL1–WDR4
Ruiz-Arroyo Victor M.•Raj Rishi•Babu Kesavan•Onolbaatar Otgonbileg•Roberts Paul H.等 6 人
Nature
2023
•2023/1/4
•Vol.613 No.7943 p.383-390
Specific, regulated modification of RNAs is important for proper gene expression1,2. tRNAs are rich with various chemical modifications that affect their stability and function3,4. 7-Methylguanosine (m7G) at tRNA position 46 is a conserved modification that modulates steady-state tRNA levels to affe...
Cryoelectron microscopyRNARNA modificationX-ray crystallography
10.1038/S41586-022-05565-5
ISSN:0028-0836
ColdstartCPI: Induced-fit theory-guided DTI predictive model with improved generalization performance
Qichang Zhao•Haochen Zhao•Linyuan Guo•Kai Zheng•Yajie Li等 9 人
Nature Communications
2025
•2025/7/11
•Vol.16 No.1 p.1-22
Predicting compound-protein interactions (CPIs) plays a crucial role in drug discovery. Traditional methods, based on the key-lock theory and rigid docking, often fail with novel compounds and proteins due to their inability to account for molecular flexibility and the high sparsity of CPI data. Her...
Computational modelsSoftwareVirtual drug screening
10.1038/S41467-025-61745-7
ISSN:2041-1723
The Mycobacterium abscessus cytochrome bcc:aa3 oxidase structure paves the way for an agent targeting subunit QcrB
Vikneswaran Mathiyazakan•Emilia Xin Yi Tan•Garrett Moraski•Sandip Basak•Wuan-Geok Saw等 7 人
Nature Communications
2026
•2026/4/3
0The cytochrome bcc:aa3 oxidase is the target of telacebec, a clinically advanced drug developed for Mycobacterium tuberculosis. However, telacebec is inactive against Mycobacterium abscessus, an opportunistic pathogen increasingly linked to chronic pulmonary infections and notoriously known for intr...
AntibioticsCryoelectron microscopy
10.1038/S41467-026-70805-5
ISSN:2041-1723
Cryo-EM structures of SARS-CoV-2 BA.2-derived subvariants spike in complex with ACE2 receptor
Yaning Li•Chang Ren•Yaping Shen•Yuanyuan Zhang•Jin Chen等 9 人
Cell Discovery
2023
•2023/11/2
•Vol.9 No.1 p.1-4
Electron microscopyMolecular biology
10.1038/S41421-023-00607-2
ISSN:2056-5968
Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features
Craig A. Magaret•Li Li•Allan C. deCamp•Morgane Rolland•Michal Juraska等 50 人
Nature Communications
2024
•2024/3/11
•Vol.15 No.1 p.1-22
In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe–critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In...
SARS-CoV-2StatisticsVaccinesViral infection
10.1038/S41467-024-46536-W
ISSN:2041-1723
Cryo-EM architecture of a near-native stretch-sensitive membrane microdomain
Jennifer M. Kefauver•Markku Hakala•Luoming Zou•Josephine Alba•Javier Espadas等 15 人
Nature
2024
•2024/7/24
•00 p.1-8
Biological membranes are partitioned into functional zones termed membrane microdomains, which contain specific lipids and proteins1–3. The composition and organization of membrane microdomains remain controversial because few techniques are available that allow the visualization of lipids in situ w...
Cryoelectron microscopyLipid signallingMembrane structure and assemblyProtein folding
10.1038/S41586-024-07720-6
ISSN:0028-0836
Reduction of DHHC5-mediated beclin 1 S-palmitoylation underlies autophagy decline in aging
Rui Guo•Jianping Liu•Xia Min•Wen Zeng•Bing Shan等 11 人
Nature Structural & Molecular Biology
2024
•2024/1/4
•00 p.1-14
Autophagy is a lysosome-dependent degradation pathway essential for cellular homeostasis, which decreases with age. However, it is unclear how aging induces autophagy decline. Here we show the role of protein S-palmitoylation in autophagy. We identify the palmitoyl acyltransferase DHHC5 as a regulat...
AgeingAutophagyPost-translational modifications
10.1038/S41594-023-01163-9
ISSN:1545-9993
Molecular basis for ubiquitin ligase CRL2 FEM1C -mediated recognition of C-degron
Xiaojie Yan•Xiaolu Wang•Yao Li•Mengqi Zhou•Yanjun Li等 9 人
Nature Chemical Biology
2021
•2021/1/4
•Vol.17 No.3 p.263-271
Proteome integrity depends on the ubiquitin–proteasome system to degrade unwanted or abnormal proteins. In addition to the N-degrons, C-terminal residues of proteins can also serve as degradation signals (C-degrons) that are recognized by specific cullin-RING ubiquitin ligases (CRLs) for proteasomal...
Post-translational modificationsProteinsX-ray crystallography
10.1038/S41589-020-00703-4
ISSN:1552-4450
An archaellum filament composed of two alternating subunits
Gambelli Lavinia•Isupov Michail N.•Conners Rebecca•McLaren Mathew•Bellack Annett等 8 人
Nature Communications
2022
•2022/2/7
•Vol.13 No.1 p.1-11
Archaea use a molecular machine, called the archaellum, to swim. The archaellum consists of an ATP-powered intracellular motor that drives the rotation of an extracellular filament composed of multiple copies of proteins named archaellins. In many species, several archaellin homologs are encoded in ...
Archaeal biologyCryoelectron microscopy
10.1038/S41467-022-28337-1
ISSN:2041-1723
RapA opens the RNA polymerase clamp to disrupt post-termination complexes and prevent cytotoxic R-loop formation
Joshua J. Brewer•Koe Inlow•Rachel A. Mooney•Barbara Bosch•Paul Dominic B. Olinares等 11 人
Nature Structural & Molecular Biology
2025
•2025/1/8
•00 p.1-11
Following transcript release during intrinsic termination, Escherichia coli RNA polymerase (RNAP) often remains associated with DNA in a post-termination complex (PTC). RNAPs in PTCs are removed from the DNA by the SWI2/SNF2 adenosine triphosphatase (ATPase) RapA. Here we determined PTC structures o...
BiochemistryCryoelectron microscopyTranscription
10.1038/S41594-024-01447-8
ISSN:1545-9993
ProtCID: a data resource for structural information on protein interactions
Qifang Xu•Roland L. Dunbrack
Nature Communications
2020
•2020/2/5
•Vol.11 No.1 p.1-16
Structural information on the interactions of proteins with other molecules is plentiful, and for some proteins and protein families, there may be 100s of available structures. It can be very difficult for a scientist who is not trained in structural bioinformatics to access this information compreh...
Computational biology and bioinformaticsDatabasesProtein databases
10.1038/S41467-020-14301-4
ISSN:2041-1723
Modifying electron injection kinetics for selective photoreduction of nitroarenes into cyclic and asymmetric azo compounds
Yang Yang•Jing Xu•Zhang Jing•Yang Fengyu•Duan Chunying
Nature Communications
2022
•2022/4/11
•Vol.13 No.1 p.1-13
Modifying the reactivity of substrates by encapsulation is essential for microenvironment catalysts. Herein, we report an alternative strategy that modifies the entry behaviour of reactants into the microenvironment and substrate inclusion thermodynamics related to the capsule to control the electro...
Bioinorganic chemistryMolecular capsules
10.1038/S41467-022-29559-Z
ISSN:2041-1723
Fast, sensitive detection of protein homologs using deep dense retrieval
Liang Hong•Zhihang Hu•Siqi Sun•Xiangru Tang•Jiuming Wang等 12 人
Nature Biotechnology
2024
•2024/8/9
•00 p.1-13
The identification of protein homologs in large databases using conventional methods, such as protein sequence comparison, often misses remote homologs. Here, we offer an ultrafast, highly sensitive method, dense homolog retriever (DHR), for detecting homologs on the basis of a protein language mode...
Protein sequence analysesProtein structure predictions
10.1038/S41587-024-02353-6
ISSN:1087-0156
CRISPR-Cas9 cytidine and adenosine base editing of splice-sites mediates highly-efficient disruption of proteins in primary and immortalized cells
Mitchell G. Kluesner•Walker S. Lahr•Cara-lin Lonetree•Branden A. Smeester•Xiaohong Qiu等 15 人
Nature Communications
2021
•2021/4/23
•Vol.12 No.1 p.1-12
CRISPR-Cas9 cytidine and adenosine base editors (CBEs and ABEs) can disrupt genes without introducing double-stranded breaks by inactivating splice sites (BE-splice) or by introducing premature stop (pmSTOP) codons. However, no in-depth comparison of these methods or a modular tool for designing BE-...
CRISPR-Cas systemsSoftwareT-cell receptorTranscriptional regulatory elements
10.1038/S41467-021-22009-2
ISSN:2041-1723
Structural basis for processive daughter-strand synthesis and proofreading by the human leading-strand DNA polymerase Pol ε
Johann J. Roske•Joseph T. P. Yeeles
Nature Structural & Molecular Biology
2024
•2024/8/7
•00 p.1-11
During chromosome replication, the nascent leading strand is synthesized by DNA polymerase epsilon (Pol ε), which associates with the sliding clamp processivity factor proliferating cell nuclear antigen (PCNA) to form a processive holoenzyme. For high-fidelity DNA synthesis, Pol ε relies on nucleoti...
Cryoelectron microscopyDNA replicationDNA synthesisReplisome
10.1038/S41594-024-01370-Y
ISSN:1545-9993
Accurate and robust protein sequence design with CarbonDesign
Milong Ren•Chungong Yu•Dongbo Bu•Haicang Zhang
Nature Machine Intelligence
2024
•2024/5/23
•Vol.6 No.5 p.536-547
Protein sequence design is critically important for protein engineering. Despite recent advancements in deep learning-based methods, achieving accurate and robust sequence design remains a challenge. Here we present CarbonDesign, an approach that draws inspiration from successful ingredients of Alph...
Machine learningProtein design
10.1038/S42256-024-00838-2
ISSN:2522-5839
Yeast- and antibody-based tools for studying tryptophan C-mannosylation
Alan John•Michael A. Järvå•Sayali Shah•Runyu Mao•Stephane Chappaz等 10 人
Nature Chemical Biology
2021
•2021/2/4
•Vol.17 No.4 p.428-437
Tryptophan C-mannosylation is an unusual co-translational protein modification performed by metazoans and apicomplexan protists. The prevalence and biological functions of this modification are poorly understood, with progress in the field hampered by a dearth of convenient tools for installing and ...
CarbohydratesGlycobiologyGlycomics
10.1038/S41589-020-00727-W
ISSN:1552-4450
Statin therapy inhibits fatty acid synthase via dynamic protein modifications
Trub Alec G.•Wagner Gregory R.•Anderson Kristin A.•Crown Scott B.•Zhang Guo-Fang等 13 人
Nature Communications
2022
•2022/5/10
•Vol.13 No.1 p.1-14
Statins are a class of drug widely prescribed for the prevention of cardiovascular disease, with pleiotropic cellular effects. Statins inhibit HMG-CoA reductase (HMGCR), which converts the metabolite HMG-CoA into mevalonate. Recent discoveries have shown HMG-CoA is a reactive metabolite that can non...
Enzyme mechanismsFat metabolismLipidsPost-translational modifications
10.1038/S41467-022-30060-W
ISSN:2041-1723
Heterochiral coupling in non-ribosomal peptide macrolactamization
Kenichi Matsuda•Rui Zhai•Takahiro Mori•Masakazu Kobayashi•Ayae Sano等 7 人
Nature Catalysis
2020
•2020/5/4
•Vol.3 No.6 p.507-515
Heterochiral coupling is favoured in abiotic peptide bond formation, whereas biotic peptide bond formation is dominated by homochiral coupling. Here, we report that heterochiral coupling is a rather general paradigm in the head-to-tail macrolactamization of non-ribosomal peptide biosynthesis. The ca...
BiocatalysisBiosynthesisEnzyme mechanismsHydrolasesPeptides
10.1038/S41929-020-0456-7
ISSN:2520-1158
Structural insights into the mechanism of rhodopsin phosphodiesterase
Tatsuya Ikuta•Wataru Shihoya•Masahiro Sugiura•Kazuho Yoshida•Masahito Watari等 12 人
Nature Communications
2020
•2020/11/5
•Vol.11 No.1 p.1-12
Rhodopsin phosphodiesterase (Rh-PDE) is an enzyme rhodopsin belonging to a recently discovered class of microbial rhodopsins with light-dependent enzymatic activity. Rh-PDE consists of the N-terminal rhodopsin domain and C-terminal phosphodiesterase (PDE) domain, connected by 76-residue linker, and ...
Biophysical chemistryEnzymesNanocrystallography
10.1038/S41467-020-19376-7
ISSN:2041-1723
Identifying T cell antigen at the atomic level with graph convolutional network
Jinhao Que•Guangfu Xue•Tao Wang•Xiyun Jin•Zuxiang Wang等 22 人
Nature Communications
2025
•2025/6/4
•Vol.16 No.1 p.1-19
Precise identification of T cell antigens in silico is crucial for the development of cancer mRNA vaccines. However, current computational methods only utilize sequence-level rather than atomic level features to identify T cell antigens, which results in poor representation of those that activate im...
Antigen processing and presentationComputational modelsMachine learningVaccines
10.1038/S41467-025-60461-6
ISSN:2041-1723
The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases
Janne J. Mäkinen•Yeonoh Shin•Eeva Vieras•Pasi Virta•Mikko Metsä-Ketelä等 7 人
Nature Communications
2021
•2021/2/4
•Vol.12 No.1 p.1-13
RNA polymerases (RNAPs) synthesize RNA from NTPs, whereas DNA polymerases synthesize DNA from 2′dNTPs. DNA polymerases select against NTPs by using steric gates to exclude the 2′OH, but RNAPs have to employ alternative selection strategies. In single-subunit RNAPs, a conserved Tyr residue discrimina...
Enzyme mechanismsTranscriptionX-ray crystallography
10.1038/S41467-021-21005-W
ISSN:2041-1723
Tracking transcription–translation coupling in real time
Nusrat Shahin Qureshi•Olivier Duss
Nature
2024
•2024/12/4
•00 p.1-9
A central question in biology is how macromolecular machines function cooperatively. In bacteria, transcription and translation occur in the same cellular compartment, and can be physically and functionally coupled1–4. Although high-resolution structures of the ribosome–RNA polymerase (RNAP) complex...
RibosomeRNASingle-molecule biophysicsStructural biologyTranscription
10.1038/S41586-024-08308-W
ISSN:0028-0836
Linker histones consolidate heterogenous nucleosome fiber contacts by linking together multiple nucleosomes
Zenita Adhireksan•Deepti Sharma•Qiuye Bao•Phoi Leng Lee•Sivaraman Padavattan等 8 人
Nature Communications
2026
•2026/3/5
0The consensus mode for linker histone (H1) association coincides with ‘on-dyad’ binding to an individual nucleosome, making it challenging to rationalize the chromatin dynamics and compacting activities of H1 in the context of a highly heterogeneous structural scaffold. Here, we investigate the acti...
Chromatin structureHistone variantsMolecular conformationNucleosomesX-ray crystallography
10.1038/S41467-026-69842-X
ISSN:2041-1723
Dual roles and evolutionary implications of P26/poxin in antagonizing intracellular cGAS-STING and extracellular melanization immunity
Yin Mengyi•Kuang Wenhua•Wang Qianran•Wang Xi•Yuan Chuanfei等 13 人
Nature Communications
2022
•2022/11/14
•Vol.13 No.1 p.1-13
P26, a homolog of the viral-encoded nuclease poxin that neutralizes the cGAS-STING innate immunity, is widely distributed in various invertebrate viruses, lepidopteran insects, and parasitoid wasps. P26/poxin from certain insect viruses also retains protease activity, though its biological role rema...
Innate immunityPathogensViral infection
10.1038/S41467-022-34761-0
ISSN:2041-1723
Inositol pyrophosphates activate the vacuolar transport chaperone complex in yeast by disrupting a homotypic SPX domain interaction
Joka Pipercevic•Bastian Kohl•Ruta Gerasimaite•Véronique Comte-Miserez•Sarah Hostachy等 11 人
Nature Communications
2023
•2023/5/8
•Vol.14 No.1 p.1-12
Many proteins involved in eukaryotic phosphate homeostasis are regulated by SPX domains. In yeast, the vacuolar transporter chaperone (VTC) complex contains two such domains, but mechanistic details of its regulation are not well understood. Here, we show at the atomic level how inositol pyrophospha...
Fungal physiologyMetabolic pathwaysProteinsSolution-state NMR
10.1038/S41467-023-38315-W
ISSN:2041-1723
Dead cells release a ‘necrosignal’ that activates antibiotic survival pathways in bacterial swarms
Souvik Bhattacharyya•David M. Walker•Rasika M. Harshey
Nature Communications
2020
•2020/8/19
•Vol.11 No.1 p.1-12
Swarming is a form of collective bacterial motion enabled by flagella on the surface of semi-solid media. Swarming populations exhibit non-genetic or adaptive resistance to antibiotics, despite sustaining considerable cell death. Here, we show that antibiotic-induced death of a sub-population benefi...
Antimicrobial resistanceBacteria
10.1038/S41467-020-17709-0
ISSN:2041-1723
Directed evolution of and structural insights into antibody-mediated disruption of a stable receptor-ligand complex
Pennington Luke F.•Gasser Pascal•Kleinboelting Silke•Zhang Chensong•Skiniotis Georgios等 7 人
Nature Communications
2021
•2021/12/3
•Vol.12 No.1 p.1-16
Antibody drugs exert therapeutic effects via a range of mechanisms, including competitive inhibition, allosteric modulation, and immune effector mechanisms. Facilitated dissociation is an additional mechanism where antibody-mediated “disruption” of stable high-affinity macromolecular complexes can p...
Protein designTranslational immunology
10.1038/S41467-021-27397-Z
ISSN:2041-1723
Structural and functional consequences of the STAT5B N642H driver mutation
Elvin D. de Araujo•Fettah Erdogan•Heidi A. Neubauer•Deniz Meneksedag-Erol•Pimyupa Manaswiyoungkul等 24 人
Nature Communications
2019
•2019/6/7
•Vol.10 No.1 p.1-15
Hyper-activated STAT5B variants are high value oncology targets for pharmacologic intervention. STAT5BN642H, a frequently-occurring oncogenic driver mutation, promotes aggressive T-cell leukemia/lymphoma in patient carriers, although the molecular origins remain unclear. Herein, we emphasize the agg...
BiochemistryCancer
10.1038/S41467-019-10422-7
ISSN:2041-1723
Quantifying and comparing radiation damage in the Protein Data Bank
Shelley Kathryn L.•Garman Elspeth F.
Nature Communications
2022
•2022/3/14
•Vol.13 No.1 p.1-11
Radiation damage remains one of the major bottlenecks to accurate structure solution in protein crystallography. It can induce structural and chemical changes in protein crystals, and is hence an important consideration when assessing the quality and biological veracity of crystal structures in repo...
ProteinsQuality controlX-ray crystallography
10.1038/S41467-022-28934-0
ISSN:2041-1723
Exploring the macrocyclic chemical space for heuristic drug design with deep learning models
Feng Hu•Xiaotong Jia•Wenjie Liao•Ziqi Chen•Hongjie Bi等 15 人
Communications Chemistry
2025
•2025/10/7
•Vol.8 No.1 p.1-11
Macrocyclic compounds hold great promise as therapeutic agents. However, their structural optimization remains constrained by the limited availability of bioactive candidates, which in turn hampers the systematic exploration of structure-activity relationships. Here we introduce CycleGPT, a generati...
Computational chemistryDrug discovery and developmentVirtual screening
10.1038/S42004-025-01686-W
ISSN:2399-3669
Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines
Wenxue Wang•Peng Wang•Chuanteng Ma•Kang Li•Zian Wang等 12 人
Nature Communications
2025
•2025/1/2
•Vol.16 No.1 p.1-10
Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, we discover a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare dimethyl...
Cryoelectron microscopyEnzymes
10.1038/S41467-024-55537-8
ISSN:2041-1723
Modulation of cardiac ryanodine receptor 2 by calmodulin
Deshun Gong•Ximin Chi•Jinhong Wei•Gewei Zhou•Gaoxingyu Huang等 10 人
Nature
2019
•2019/7/5
•Vol.572 No.7769 p.347-351
The high-conductance intracellular calcium (Ca2+) channel RyR2 is essential for the coupling of excitation and contraction in cardiac muscle. Among various modulators, calmodulin (CaM) regulates RyR2 in a Ca2+-dependent manner. Here we reveal the regulatory mechanism by which porcine RyR2 is modulat...
Cryoelectron microscopyPermeation and transport
10.1038/S41586-019-1377-Y
ISSN:0028-0836
A poly(thymine)–melamine duplex for the assembly of DNA nanomaterials
Qian Li•Jiemin Zhao•Longfei Liu•Sagun Jonchhe•Felix J. Rizzuto等 11 人
Nature Materials
2020
•2020/7/13
•Vol.19 No.9 p.1012-1018
The diversity of DNA duplex structures is limited by a binary pair of hydrogen-bonded motifs. Here we show that poly(thymine) self-associates into antiparallel, right-handed duplexes in the presence of melamine, a small molecule that presents a triplicate set of the hydrogen-bonding face of adenine....
DNA nanostructuresSelf-assembly
10.1038/S41563-020-0728-2
ISSN:1476-1122
Rational engineering of allosteric protein switches by in silico prediction of domain insertion sites
Benedict Wolf•Pegi Shehu•Luca Brenker•Anna-Lisa von Bachmann•Ann-Sophie Kroell等 11 人
Nature Methods
2025
•2025/8/4
•Vol.22 No.8 p.1698-1706
Domain insertion engineering is a powerful approach to juxtapose otherwise separate biological functions, resulting in proteins with new-to-nature activities. A prominent example are switchable protein variants, created by receptor domain insertion into effector proteins. Identifying suitable, allos...
Protein designSynthetic biology
10.1038/S41592-025-02741-Z
ISSN:1548-7091
Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes
Nature Neuroscience
2024
•2024/10/3
•Vol.27 No.10 p.1864-1879
Identifying genetic risk factors for highly heterogeneous disorders such as epilepsy remains challenging. Here we present, to our knowledge, the largest whole-exome sequencing study of epilepsy to date, with more than 54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple ge...
Computational biology and bioinformaticsEpilepsyGeneticsGenome-wide association studies
10.1038/S41593-024-01747-8
ISSN:1097-6256
A pocket-escaping design to prevent the common interference with near-infrared fluorescent probes in vivo
Panfei Xing•Yiming Niu•Ruoyu Mu•Zhenzhen Wang•Daping Xie等 8 人
Nature Communications
2020
•2020/3/26
•Vol.11 No.1 p.1-9
Near-infrared (NIR) fluorescent probes are among the most attractive chemical tools for biomedical imaging. However, their in vivo applications are hindered by albumin binding, generating unspecific fluorescence that masks the specific signal from the analyte. Here, combining experimental and dockin...
Analytical biochemistryChemical toolsImagingSensors and probesChemical synthesis
10.1038/S41467-020-15323-8
ISSN:2041-1723
DNA mechanical flexibility controls DNA potential to activate cGAS-mediated immune surveillance
Wang Lina•Li Siru•Wang Kai•Wang Na•Liu Qiaoling等 12 人
Nature Communications
2022
•2022/11/19
•Vol.13 No.1 p.1-18
DNA is well-documented to stimulate immune response. However, the nature of the DNA to activate immune surveillance is less understood. Here, we show that the activation of cyclic GMP-AMP synthase (cGAS) depends on DNA mechanical flexibility, which is controlled by DNA-sequence, -damage and -length....
DNAEnzyme mechanismsInnate immunity
10.1038/S41467-022-34858-6
ISSN:2041-1723
Inhibition of tyrosine kinase BMX increases cell death in response to existing chemotherapeutic agents overcoming apoptotic resistance in cancer
Dalal Morad•Sam Skinner•Karen Bowman•Chitra Seewooruthun•Joanna L. Fox
Cell Death & Disease
2025
•2025/11/10
•Vol.16 No.1 p.8130
BMX tyrosine kinase has emerged as a novel drug target, the inhibition of which simultaneously decreases proliferative signaling and increases cell death. BMX expression is upregulated in numerous cancers and causes acquired resistance to chemotherapeutic drugs. In addition to being responsive to mu...
Breast cancerTarget validation
10.1038/S41419-025-08131-9
ISSN:2041-4889
Structural snapshots of the minimal PKS system responsible for octaketide biosynthesis
Alois Bräuer•Qiuqin Zhou•Gina L. C. Grammbitter•Maximilian Schmalhofer•Michael Rühl等 8 人
Nature Chemistry
2020
•2020/7/6
•Vol.12 No.8 p.755-763
Type II polyketide synthases (PKSs) are multi-enzyme complexes that produce secondary metabolites of medical relevance. Chemical backbones of such polyketides are produced by minimal PKS systems that consist of a malonyl transacylase, an acyl carrier protein and an α/β heterodimeric ketosynthase. He...
NanocrystallographyNatural product synthesis
10.1038/S41557-020-0491-7
ISSN:1755-4330
Learning on topological surface and geometric structure for 3D molecular generation
Odin Zhang•Tianyue Wang•Gaoqi Weng•Dejun Jiang•Ning Wang等 15 人
Nature Computational Science
2023
•2023/10/9
•Vol.3 No.10 p.849-859
Highly effective de novo design is a grand challenge of computer-aided drug discovery. Practical structure-specific three-dimensional molecule generations have started to emerge in recent years, but most approaches treat the target structure as a conditional input to bias the molecule generation and...
CheminformaticsComputational chemistryDrug discovery
10.1038/S43588-023-00530-2
ISSN:2662-8457
Cryo-EM structure and protease activity of the type III-E CRISPR-Cas effector
Huo Yangao•Zhao Hongshen•Dong Qinghua•Jiang Tao
Nature Microbiology
2023
•2023/1/26
•Vol.8 No.3 p.522-532
The recently discovered type III-E CRISPR-Cas effector Cas7-11 shows promise when used as an RNA manipulation tool, but its structure and the mechanisms underlying its function remain unclear. Here we present four cryo-EM structures of Desulfonema ishimotonii Cas7-11-crRNA complex in pre-target and ...
Cryoelectron microscopyRNA editing
10.1038/S41564-022-01316-4
ISSN:2058-5276
FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth
Niu Mengmeng•Xu Jing•Liu Yang•Li Yuhuang•He Tao等 30 人
Nature Communications
2021
•2021/10/11
•Vol.12 No.1 p.1-15
Abnormal activation of epidermal growth factor receptor (EGFR) drives non-small cell lung cancer (NSCLC) development. EGFR mutations-mediated resistance to tyrosine-kinase inhibitors (TKIs) is a major hurdle for NSCLC treatment. Here, we show that F-box protein FBXL2 targets EGFR and EGFR TKI-resist...
Growth factor signallingNon-small-cell lung cancerUbiquitylation
10.1038/S41467-021-26222-X
ISSN:2041-1723
Structure and function of the metagenomic plastic-degrading polyester hydrolase PHL7 bound to its product
Richter P. Konstantin•Blázquez-Sánchez Paula•Zhao Ziyue•Engelberger Felipe•Wiebeler Christian等 15 人
Nature Communications
2023
•2023/4/5
•Vol.14 No.1 p.1-11
The recently discovered metagenomic-derived polyester hydrolase PHL7 is able to efficiently degrade amorphous polyethylene terephthalate (PET) in post-consumer plastic waste. We present the cocrystal structure of this hydrolase with its hydrolysis product terephthalic acid and elucidate the influenc...
BiotechnologyX-ray crystallography
10.1038/S41467-023-37415-X
ISSN:2041-1723
Structural insights into β-1,3-glucan cleavage by a glycoside hydrolase family
Camila R. Santos•Pedro A. C. R. Costa•Plínio S. Vieira•Sinkler E. T. Gonzalez•Thamy L. R. Correa等 19 人
Nature Chemical Biology
2020
•2020/5/25
•Vol.16 No.8 p.920-929
The fundamental and assorted roles of β-1,3-glucans in nature are underpinned on diverse chemistry and molecular structures, demanding sophisticated and intricate enzymatic systems for their processing. In this work, the selectivity and modes of action of a glycoside hydrolase family active on β-1,3...
CarbohydratesGlycobiologyX-ray crystallography
10.1038/S41589-020-0554-5
ISSN:1552-4450
An ARF6–Exportin-5 axis delivers pre-miRNA cargo to tumour microvesicles
James W. Clancy•Ye Zhang•Colin Sheehan•Crislyn D’Souza-Schorey
Nature Cell Biology
2019
•2019/6/24
•Vol.21 No.7 p.856-866
Tumour-derived microvesicles (TMVs) comprise a class of extracellular vesicles released from tumour cells that are now understood to facilitate communication between the tumour and the surrounding microenvironment. Despite their significance, the regulatory mechanisms governing the trafficking of bi...
Membrane traffickingmiRNAsNuclear transport
10.1038/S41556-019-0345-Y
ISSN:1465-7392
Activation pathway of a G protein-coupled receptor uncovers conformational intermediates as targets for allosteric drug design
Lu Shaoyong•He Xinheng•Yang Zhao•Chai Zongtao•Zhou Shuhua等 11 人
Nature Communications
2021
•2021/8/5
•Vol.12 No.1 p.1-15
G protein-coupled receptors (GPCRs) are the most common proteins targeted by approved drugs. A complete mechanistic elucidation of large-scale conformational transitions underlying the activation mechanisms of GPCRs is of critical importance for therapeutic drug development. Here, we apply a combine...
Communicating chemistryProtein function predictions
10.1038/S41467-021-25020-9
ISSN:2041-1723
Binding affinity estimation from restrained umbrella sampling simulations
Govind Kumar Vivek•Polasa Adithya•Agrawal Shilpi•Kumar Thallapuranam Krishnaswamy Suresh•Moradi Mahmoud
Nature Computational Science
2022
•2022/12/29
•Vol.3 No.1 p.59-70
The protein–ligand binding affinity quantifies the binding strength between a protein and its ligand. Computer modeling and simulations can be used to estimate the binding affinity or binding free energy using data- or physics-driven methods or a combination thereof. Here we discuss a purely physics...
Biophysical chemistryComputational biophysics
10.1038/S43588-022-00389-9
ISSN:2662-8457
RNA–ligand interaction scoring via data perturbation and augmentation modeling
Hongli Ma•Letian Gao•Yunfan Jin•Jianwei Ma•Yilan Bai等 10 人
Nature Computational Science
2025
•2025/6/24
•00 p.1-13
Despite recent advances in RNA-targeting drug discovery, the development of data-driven deep learning models remains challenging owing to limited validated RNA–small molecule interaction data and scarce known RNA structures. In this context, we introduce RNAsmol, a sequence-based deep learning frame...
Computational biology and bioinformaticsDrug discovery
10.1038/S43588-025-00820-X
ISSN:2662-8457
Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase
Chongyang Wang•Changshui Liu•Xiaochuan Zhu•Quancai Peng•Qingjun Ma
Nature Communications
2023
•2023/8/9
•Vol.14 No.1 p.1-11
Although enzyme catalysis is typified by high specificity, enzymes can catalyze various substrates (substrate promiscuity) and/or different reaction types (catalytic promiscuity) using a single active site. This interesting phenomenon is widely distributed in enzyme catalysis, with both fundamental ...
Enzyme mechanismsEnzymesX-ray crystallography
10.1038/S41467-023-40455-Y
ISSN:2041-1723
Orthogonalized human protease control of secreted signals
Carlos A. Aldrete•Connor C. Call•Lucas E. Sant’Anna•Alexander E. Vlahos•Jimin Pei等 7 人
Nature Chemical Biology
2025
•2025/1/15
•00 p.1-10
Synthetic circuits that regulate protein secretion in human cells could support cell-based therapies by enabling control over local environments. Although protein-level circuits enable such potential clinical applications, featuring orthogonality and compactness, their non-human origin poses a poten...
Cell signallingProteasesSynthetic biology
10.1038/S41589-024-01831-X
ISSN:1552-4450
Mechanisms of NLRP3 activation and inhibition elucidated by functional analysis of disease-associated variants
Shouya Feng•Matthew C. Wierzbowski•Katja Hrovat-Schaale•Andreas Dumortier•Yaoyuan Zhang等 18 人
Nature Immunology
2025
•2025/2/10
•Vol.26 No.3 p.511-523
The NLRP3 inflammasome is a multiprotein complex that mediates caspase-1 activation and the release of proinflammatory cytokines, including interleukin (IL)-1β and IL-18. Gain-of-function variants in the gene encoding NLRP3 (also called cryopyrin) lead to constitutive inflammasome activation and exc...
Autoinflammatory syndromeInflammasomeNOD-like receptors
10.1038/S41590-025-02088-9
ISSN:1529-2908
RNAbpFlow: base pair-augmented SE(3) flow matching for conditional RNA 3D structure generation
Sumit Tarafder•Debswapna Bhattacharya
Nature Methods
2026
•2026/6/30
•00 p.1-10
Despite the groundbreaking advances in deep learning-enabled methods for biomolecular modeling, predicting accurate three-dimensional (3D) structures of RNA remains challenging owing to the highly flexible nature of RNA molecules combined with the limited availability of evolutionary sequences or st...
Computational modelsMachine learning
10.1038/S41592-026-03128-4
ISSN:1548-7091
Secretory quality control constrains functional selection-associated protein structure innovation
Cheng Bin•Lv Jian-Min•Liang Yu-Lin•Zhu Li•Huang Xiao-Ping等 9 人
Communications Biology
2022
•2022/3/25
•Vol.5 No.1 p.1-10
Biophysical models suggest a dominant role of structural over functional constraints in shaping protein evolution. Selection on structural constraints is linked closely to expression levels of proteins, which together with structure-associated activities determine in vivo functions of proteins. Here...
Molecular evolutionPattern recognition receptors
10.1038/S42003-022-03220-3
ISSN:2399-3642
Axonemal structures reveal mechanoregulatory and disease mechanisms
Travis Walton•Miao Gui•Simona Velkova•Mahmoud R. Fassad•Robert A. Hirst等 11 人
Nature
2023
•2023/5/31
•00 p.1-9
Motile cilia and flagella beat rhythmically on the surface of cells to power the flow of fluid and to enable spermatozoa and unicellular eukaryotes to swim. In humans, defective ciliary motility can lead to male infertility and a congenital disorder called primary ciliary dyskinesia (PCD), in w...
CiliaCryoelectron microscopyDyneinInfertilityRespiratory tract diseases
10.1038/S41586-023-06140-2
ISSN:0028-0836
Synthesis and direct assay of large macrocycle diversities by combinatorial late-stage modification at picomole scale
Habeshian Sevan•Merz Manuel Leonardo•Sangouard Gontran•Mothukuri Ganesh Kumar•Schüttel Mischa等 13 人
Nature Communications
2022
•2022/7/2
•Vol.13 No.1 p.1-14
Macrocycles have excellent potential as therapeutics due to their ability to bind challenging targets. However, generating macrocycles against new targets is hindered by a lack of large macrocycle libraries for high-throughput screening. To overcome this, we herein established a combinatorial approa...
Combinatorial librariesHigh-throughput screeningPeptidesScreening
10.1038/S41467-022-31428-8
ISSN:2041-1723
A mechanistic framework for the recognition of chemically diverse brassinosteroids by BRI1-family receptor kinases
Alberto Caregnato•Houming Chen•Miroslav Kvasnica•Ulrich Hohmann•Jana Oklestkova等 10 人
Nature Plants
2026
•2026/8/5
•00 p.1-17
Brassinosteroids (BRs) are chemically diverse plant steroid hormones produced via a branched biosynthetic pathway. The potent BR brassinolide is sensed by the membrane receptor kinase BRI1 and a SERK co-receptor, but the physiological functions of other abundant BRs remain to be characterized. Here ...
Biochemical assaysBrassinosteroidGenetic engineeringPlant signallingX-ray crystallography
10.1038/S41477-026-02346-0
ISSN:2055-0278
Structural insights into the broad protection against H1 influenza viruses by a computationally optimized hemagglutinin vaccine
Dzimianski John V.•Han Julianna•Sautto Giuseppe A.•O’Rourke Sara M.•Cruz Joseph M.等 13 人
Communications Biology
2023
•2023/4/25
•Vol.6 No.1 p.1-13
Influenza virus poses an ongoing human health threat with pandemic potential. Due to mutations in circulating strains, formulating effective vaccines remains a challenge. The use of computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) proteins is a promising vaccine strategy...
Structural biologyVaccines
10.1038/S42003-023-04793-3
ISSN:2399-3642
Benchmarking AI-powered docking methods from the perspective of virtual screening
Shukai Gu•Chao Shen•Xujun Zhang•Huiyong Sun•Heng Cai等 16 人
Nature Machine Intelligence
2025
•2025/2/13
•00 p.1-12
Recently, many artificial intelligence (AI)-powered protein–ligand docking and scoring methods have been developed, demonstrating impressive speed and accuracy. However, these methods often neglected the physical plausibility of the docked complexes and their efficacy in virtual screening (VS) proje...
CheminformaticsMachine learningVirtual drug screening
10.1038/S42256-025-00993-0
ISSN:2522-5839
Structural insights into selective small molecule activation of PKG1α
Essam Metwally•Victor Mak•Aileen Soriano•Matthias Zebisch•H. Leonardo Silvestre等 18 人
Communications Biology
2023
•2023/7/31
•Vol.6 No.1 p.1-13
cGMP-dependent protein kinase I-α (PKG1α) is a target for pulmonary arterial hypertension due to its role in the regulation of smooth muscle function. While most work has focused on regulation of cGMP turnover, we recently described several small molecule tool compounds which were capable of activat...
KinasesMolecular modellingTarget validationX-ray crystallography
10.1038/S42003-023-05095-4
ISSN:2399-3642
Semi-inductive dataset construction and framework optimization for practical drug target interaction prediction with ScopeDTI
Yigang Chen•Xiang Ji•Ziyue Zhang•Zihao Zhu•Yuming Zhou等 20 人
Nature Communications
2025
•2025/12/13
0Deep learning-based drug-target interaction (DTI) prediction methods have demonstrated strong performance; however, real-world applicability remains constrained by limited data diversity and modeling complexity. To address these challenges, we propose SCOPE-DTI, a unified framework combining a large...
Computational modelsData integrationMachine learningTarget identificationVirtual drug screening
10.1038/S41467-025-66311-9
ISSN:2041-1723
Structural determinants of DNA recognition by the NO sensor NsrR and related Rrf2-type [FeS]-transcription factors
Rohac Roman•Crack Jason C.•de Rosny Eve•Gigarel Océane•Le Brun Nick E.等 7 人
Communications Biology
2022
•2022/7/30
•Vol.5 No.1 p.1-11
Several transcription factors of the Rrf2 family use an iron-sulfur cluster to regulate DNA binding through effectors such as nitric oxide (NO), cellular redox status and iron levels. [4Fe-4S]-NsrR from Streptomyces coelicolor (ScNsrR) modulates expression of three different genes via reaction and c...
DNAMetalloproteinsTranscriptionX-ray crystallography
10.1038/S42003-022-03745-7
ISSN:2399-3642
Probing the modulation of enzyme kinetics by multi-temperature, time-resolved serial crystallography
Eike C. Schulz•Andreas Prester•David von Stetten•Gargi Gore•Caitlin E. Hatton等 11 人
Nature Communications
2025
•2025/7/16
•Vol.16 No.1 p.1-12
The vast majority of protein structures are determined at cryogenic temperatures, which are far from physiological conditions. Nevertheless, it is well established that temperature is an essential thermodynamic parameter for understanding the conformational dynamics and functionality of proteins in ...
Biophysical chemistryMolecular biophysicsX-ray crystallography
10.1038/S41467-025-61631-2
ISSN:2041-1723
Enhancing antibody affinity through experimental sampling of non-deleterious CDR mutations predicted by machine learning
Thomas Clark•Vidya Subramanian•Akila Jayaraman•Emmett Fitzpatrick•Ranjani Gopal等 12 人
Communications Chemistry
2023
•2023/11/9
•Vol.6 No.1 p.1-13
The application of machine learning (ML) models to optimize antibody affinity to an antigen is gaining prominence. Unfortunately, the small and biased nature of the publicly available antibody-antigen interaction datasets makes it challenging to build an ML model that can accurately predict binding ...
Antibody therapyComputational chemistryProtein design
10.1038/S42004-023-01037-7
ISSN:2399-3669
Concerted dynamics of metallo-base pairs in an A/B-form helical transition
Olivia P. Schmidt•Simon Jurt•Silke Johannsen•Ashkan Karimi•Roland K. O. Sigel等 6 人
Nature Communications
2019
•2019/10/23
•Vol.10 No.1 p.1-11
Metal-mediated base pairs expand the repertoire of nucleic acid structures and dynamics. Here we report solution structures and dynamics of duplex DNA containing two all-natural C-HgII-T metallo base pairs separated by six canonical base pairs. NMR experiments reveal a 3:1 ratio of well-resolved str...
Biophysical chemistrySolution-state NMR
10.1038/S41467-019-12440-X
ISSN:2041-1723
Inhibition of NMDA receptors through a membrane-to-channel path
Wilcox Madeleine R.•Nigam Aparna•Glasgow Nathan G.•Narangoda Chamali•Phillips Matthew B.等 11 人
Nature Communications
2022
•2022/7/15
•Vol.13 No.1 p.1-15
N-methyl-d-aspartate receptors (NMDARs) are transmembrane proteins that are activated by the neurotransmitter glutamate and are found at most excitatory vertebrate synapses. NMDAR channel blockers, an antagonist class of broad pharmacological and clinical significance, inhibit by occluding the NMDAR...
Ion channels in the nervous systemMolecular neuroscienceReceptor pharmacology
10.1038/S41467-022-31817-Z
ISSN:2041-1723
A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation
Juan Manuel Valverde•Geronimo Dubra•Michael Phillips•Austin Haider•Carlos Elena-Real等 23 人
Nature Communications
2023
•2023/10/9
•Vol.14 No.1 p.1-23
Cell cycle transitions result from global changes in protein phosphorylation states triggered by cyclin-dependent kinases (CDKs). To understand how this complexity produces an ordered and rapid cellular reorganisation, we generated a high-resolution map of changing phosphosites throughout unperturbe...
Cell biologyPhosphorylationProtein–protein interaction networks
10.1038/S41467-023-42049-0
ISSN:2041-1723
Covalent penicillin-protein conjugates elicit anti-drug antibodies that are clonally and functionally restricted
Lachlan P. Deimel•Lucile Moynié•Guoxuan Sun•Viliyana Lewis•Abigail Turner等 17 人
Nature Communications
2024
•2024/8/10
•Vol.15 No.1 p.1-12
Many archetypal and emerging classes of small-molecule therapeutics form covalent protein adducts. In vivo, both the resulting conjugates and their off-target side-conjugates have the potential to elicit antibodies, with implications for allergy and drug sequestration. Although β-lactam antibiotics ...
AntibodiesChemical biologyImmunologyNMR spectroscopyStructural biology
10.1038/S41467-024-51138-7
ISSN:2041-1723
Structural insights into catalytic mechanism and product delivery of cyanobacterial acyl-acyl carrier protein reductase
Yu Gao•Hongmei Zhang•Minrui Fan•Chenjun Jia•Lifang Shi等 10 人
Nature Communications
2020
•2020/3/23
•Vol.11 No.1 p.1-11
Long-chain alk(a/e)nes represent the major constituents of conventional transportation fuels. Biosynthesis of alkanes is ubiquitous in many kinds of organisms. Cyanobacteria possess two enzymes, acyl-acyl carrier protein (acyl-ACP) reductase (AAR) and aldehyde-deformylating oxygenase (ADO), which fu...
BioenergeticsBiofuelsStructural biologyX-ray crystallography
10.1038/S41467-020-15268-Y
ISSN:2041-1723
Structural insights into hepatitis C virus receptor binding and entry
Kumar Ashish•Hossain Reafa A.•Yost Samantha A.•Bu Wei•Wang Yuanyuan等 9 人
Nature
2021
•2021/9/15
•00 p.1-5
Hepatitis C virus (HCV) infection is a causal agent of chronic liver disease, cirrhosis and hepatocellular carcinoma in humans, and afflicts more than 70 million people worldwide. The HCV envelope glycoproteins E1 and E2 are responsible for the binding of the virus to the host cell, but the exact en...
Hepatitis C virusX-ray crystallography
10.1038/S41586-021-03913-5
ISSN:0028-0836
USP5-Beclin 1 axis overrides p53-dependent senescence and drives Kras-induced tumorigenicity
Li Juan•Wang Yang•Luo Yue•Liu Yang•Yi Yong等 16 人
Nature Communications
2022
•2022/12/17
•Vol.13 No.1 p.1-15
Non-small cell lung cancers (NSCLC) frequently contain KRAS mutation but retain wild-type TP53. Abundant senescent cells are observed in premalignant but not in malignant tumors derived from the Kras-driven mouse model, suggesting that KRAS oncogenic signaling would have to overcome the intrinsic se...
AutophagyDeubiquitylating enzymesNon-small-cell lung cancerSenescenceTumour-suppressor proteins
10.1038/S41467-022-35557-Y
ISSN:2041-1723
Probing altered receptor specificities of antigenically drifting human H3N2 viruses by chemoenzymatic synthesis, NMR, and modeling
Luca Unione•Augustinus N. A. Ammerlaan•Gerlof P. Bosman•Elif Uslu•Ruonan Liang等 17 人
Nature Communications
2024
•2024/4/6
•Vol.15 No.1 p.1-12
Prototypic receptors for human influenza viruses are N-glycans carrying α2,6-linked sialosides. Due to immune pressure, A/H3N2 influenza viruses have emerged with altered receptor specificities that bind α2,6-linked sialosides presented on extended N-acetyl-lactosamine (LacNAc) chains. Here, binding...
GlycobiologyInfluenza virusSolution-state NMR
10.1038/S41467-024-47344-Y
ISSN:2041-1723
Essential dynamic interdependence of FtsZ and SepF for Z-ring and septum formation in Corynebacterium glutamicum
Adrià Sogues•Mariano Martinez•Quentin Gaday•Mathilde Ben Assaya•Martin Graña等 14 人
Nature Communications
2020
•2020/4/2
•Vol.11 No.1 p.1-14
The mechanisms of Z-ring assembly and regulation in bacteria are poorly understood, particularly in non-model organisms. Actinobacteria, a large bacterial phylum that includes the pathogen Mycobacterium tuberculosis, lack the canonical FtsZ-membrane anchors and Z-ring regulators described for E. col...
Bacterial physiologyCell divisionCytoskeletal proteinsX-ray crystallography
10.1038/S41467-020-15490-8
ISSN:2041-1723
Structural mechanisms for binding and activation of a contact-quenched fluorophore by RhoBAST
Yufan Zhang•Zhonghe Xu•Yu Xiao•Haodong Jiang•Xiaobing Zuo等 7 人
Nature Communications
2024
•2024/5/17
•Vol.15 No.1 p.1-14
The fluorescent light-up aptamer RhoBAST, which binds and activates the fluorophore–quencher conjugate tetramethylrhodamine-dinitroaniline with high affinity, super high brightness, remarkable photostability, and fast exchange kinetics, exhibits excellent performance in super-resolution RNA imaging....
ImagingSAXSX-ray crystallography
10.1038/S41467-024-48478-9
ISSN:2041-1723
Unravelling the mechanism of neurotensin recognition by neurotensin receptor 1
Kazem Asadollahi•Sunnia Rajput•Lazarus Andrew de Zhang•Ching-Seng Ang•Shuai Nie等 12 人
Nature Communications
2023
•2023/12/9
•Vol.14 No.1 p.1-13
The conformational ensembles of G protein-coupled receptors (GPCRs) include inactive and active states. Spectroscopy techniques, including NMR, show that agonists, antagonists and other ligands shift the ensemble toward specific states depending on the pharmacological efficacy of the ligand. How rec...
Biophysical chemistryG protein-coupled receptorsSolution-state NMR
10.1038/S41467-023-44010-7
ISSN:2041-1723
Fragment-based discovery enables direct targeting of the melanoma oncogene MITF
Deborah Castelletti•Jürgen Hinrichs•Goran Malojčić•Fei Ji•Aurore Desplat等 33 人
Nature Communications
2025
•2025/12/9
0Despite the improvement of therapeutic options, melanoma patients with advanced metastatic disease are still in high need of durable treatments. Analysis of clinical data from patients receiving targeted and/or immunotherapy, along with genetic and functional studies in preclinical melanoma models, ...
Computational biophysicsMelanomaMolecular conformationStructure-based drug designX-ray crystallography
10.1038/S41467-025-67297-0
ISSN:2041-1723
Structure-based prediction and characterization of photo-crosslinking in native protein–RNA complexes
Huijuan Feng•Xiang-Jun Lu•Suvrajit Maji•Linxi Liu•Dmytro Ustianenko等 7 人
Nature Communications
2024
•2024/3/13
•Vol.15 No.1 p.1-14
UV-crosslinking of protein and RNA in direct contacts has been widely used to study protein-RNA complexes while our understanding of the photo-crosslinking mechanisms remains poor. This knowledge gap is due to the challenge of precisely mapping the crosslink sites in protein and RNA simultaneously i...
Computational biology and bioinformaticsRNARNA-binding proteinsStructural biology
10.1038/S41467-024-46429-Y
ISSN:2041-1723
Prime editing with genuine Cas9 nickases minimizes unwanted indels
Lee Jaesuk•Lim Kayeong•Kim Annie•Mok Young Geun•Chung Eugene等 8 人
Nature Communications
2023
•2023/3/30
•Vol.14 No.1 p.1-11
Unlike CRISPR-Cas9 nucleases, which yield DNA double-strand breaks (DSBs), Cas9 nickases (nCas9s), which are created by replacing key catalytic amino-acid residues in one of the two nuclease domains of S. pyogenesis Cas9 (SpCas9), produce nicks or single-strand breaks. Two SpCas9 variants, namely, n...
CRISPR-Cas9 genome editingDNA recombination
10.1038/S41467-023-37507-8
ISSN:2041-1723
Structural and biochemical evidence that ATP inhibits the cancer biomarker human aldehyde dehydrogenase 1A3
Castellví Albert•Pequerul Raquel•Barracco Vito•Juanhuix Judith•Parés Xavier等 6 人
Communications Biology
2022
•2022/4/13
•Vol.5 No.1 p.1-12
Human aldehyde dehydrogenase (ALDH) participates in the oxidative stress response and retinoid metabolism, being involved in several diseases, including cancer, diabetes and obesity. The ALDH1A3 isoform has recently elicited wide interest because of its potential use as a cancer stem cell biomarker ...
OxidoreductasesX-ray crystallography
10.1038/S42003-022-03311-1
ISSN:2399-3642
Targeted degradation via direct 26S proteasome recruitment
Bashore Charlene•Prakash Sumit•Johnson Matthew C.•Conrad Ryan J.•Kekessie Ivy A.等 25 人
Nature Chemical Biology
2022
•2022/12/28
•Vol.19 No.1 p.55-63
Engineered destruction of target proteins by recruitment to the cell’s degradation machinery has emerged as a promising strategy in drug discovery. The majority of molecules that facilitate targeted degradation do so via a select number of ubiquitin ligases, restricting this therapeutic approach to ...
Chemical toolsPeptidesTarget identification
10.1038/S41589-022-01218-W
ISSN:1552-4450
Structure of the metastatic factor P-Rex1 reveals a two-layered autoinhibitory mechanism
Chang Yong-Gang•Lupton Christopher J.•Bayly-Jones Charles•Keen Alastair C.•D’Andrea Laura等 12 人
Nature Structural & Molecular Biology
2022
•2022/7/21
•Vol.29 No.8 p.767-773
P-Rex (PI(3,4,5)P3-dependent Rac exchanger) guanine nucleotide exchange factors potently activate Rho GTPases. P-Rex guanine nucleotide exchange factors are autoinhibited, synergistically activated by Gβγ and PI(3,4,5)P3 binding and dysregulated in cancer. Here, we use X-ray crystallography, cryogen...
Cryoelectron microscopyX-ray crystallography
10.1038/S41594-022-00804-9
ISSN:1545-9993
Immunogenicity and therapeutic targeting of a public neoantigen derived from mutated PIK3CA
Chandran Smita S.•Ma Jiaqi•Klatt Martin G.•Dündar Friederike•Bandlamudi Chaitanya等 22 人
Nature Medicine
2022
•2022/4/28
•00 p.1-12
Public neoantigens (NeoAgs) represent an elite class of shared cancer-specific epitopes derived from recurrently mutated driver genes. Here we describe a high-throughput platform combining single-cell transcriptomic and T cell receptor (TCR) sequencing to establish whether mutant PIK3CA, among the m...
Cancer immunotherapySequencingT cellsTumour immunology
10.1038/S41591-022-01786-3
ISSN:1078-8956
Structure of the human LAT1–4F2hc heteromeric amino acid transporter complex
Renhong Yan•Xin Zhao•Jianlin Lei•Qiang Zhou
Nature
2019
•2019/3/13
•Vol.568 No.7750 p.127-130
The L-type amino acid transporter 1 (LAT1; also known as SLC7A5) catalyses the cross-membrane flux of large neutral amino acids in a sodium- and pH-independent manner1–3. LAT1, an antiporter of the amino acid–polyamine–organocation superfamily, also catalyses the permeation of thyroid hormones, phar...
Cryoelectron microscopyMembrane proteins
10.1038/S41586-019-1011-Z
ISSN:0028-0836
Staufen2-mediated RNA recognition and localization requires combinatorial action of multiple domains
Simone Heber•Imre Gáspár•Jan-Niklas Tants•Johannes Günther•Sandra M. Fernandez Moya等 9 人
Nature Communications
2019
•2019/4/10
•Vol.10 No.1 p.1-16
Throughout metazoans, Staufen (Stau) proteins are core factors of mRNA localization particles. They consist of three to four double-stranded RNA binding domains (dsRBDs) and a C-terminal dsRBD-like domain. Mouse Staufen2 (mStau2)-like Drosophila Stau (dmStau) contains four dsRBDs. Existing data sugg...
BiochemistryMolecular biologyRNA-binding proteinsStructural biology
10.1038/S41467-019-09655-3
ISSN:2041-1723
Concerted transformation of a hyper-paused transcription complex and its reinforcing protein
Philipp K. Zuber•Nelly Said•Tarek Hilal•Bing Wang•Bernhard Loll等 11 人
Nature Communications
2024
•2024/4/8
•Vol.15 No.1 p.1-19
RfaH, a paralog of the universally conserved NusG, binds to RNA polymerases (RNAP) and ribosomes to activate expression of virulence genes. In free, autoinhibited RfaH, an α-helical KOW domain sequesters the RNAP-binding site. Upon recruitment to RNAP paused at an ops site, KOW is released and refol...
Cryoelectron microscopyTranscriptional regulatory elements
10.1038/S41467-024-47368-4
ISSN:2041-1723
Fragment-based drug design of a bacterial kinase inhibitor capable of increasing the antibiotic sensitivity of clinical isolates
Julien Kowalewski•Robin Deutscher•Marion Richardoz•Mathilde Tomaszczyk•Muriel Gelin等 11 人
Communications Chemistry
2025
•2025/11/27
0According to the World Health Organization (WHO), antimicrobial resistance is a serious global health issue. Overcoming antibiotic resistance involves several strategies, including the inhibition of resistance mechanisms. Among the various resistance mechanisms, aminoglycoside phosphotransferases (A...
Drug screeningKinasesScreeningTransferasesX-ray crystallography
10.1038/S42004-025-01795-6
ISSN:2399-3669
ADP binding by the Culex quinquefasciatus mosquito D7 salivary protein enhances blood feeding on mammals
Ines Martin-Martin•Andrew Paige•Paola Carolina Valenzuela Leon•Apostolos G. Gittis•Olivia Kern等 11 人
Nature Communications
2020
•2020/6/9
•Vol.11 No.1 p.1-15
During blood-feeding, mosquito saliva is injected into the skin to facilitate blood meal acquisition. D7 proteins are among the most abundant components of the mosquito saliva. Here we report the ligand binding specificity and physiological relevance of two D7 long proteins from Culex quinquefasciat...
EntomologyNucleotide-binding proteinsX-ray crystallography
10.1038/S41467-020-16665-Z
ISSN:2041-1723
Molecular basis for DarT ADP-ribosylation of a DNA base
Schuller Marion•Butler Rachel E.•Ariza Antonio•Tromans-Coia Callum•Jankevicius Gytis等 10 人
Nature
2021
•2021/8/18
•00 p.1-6
ADP-ribosyltransferases use NAD+ to catalyse substrate ADP-ribosylation1, and thereby regulate cellular pathways or contribute to toxin-mediated pathogenicity of bacteria2–4. Reversible ADP-ribosylation has traditionally been considered a protein-specific modification5, but recent in vitro studies h...
DNA damage and repairDNA repair enzymesPathogensX-ray crystallography
10.1038/S41586-021-03825-4
ISSN:0028-0836
TEFM variants impair mitochondrial transcription causing childhood-onset neurological disease
Van Haute Lindsey•O’Connor Emily•Díaz-Maldonado Héctor•Munro Benjamin•Polavarapu Kiran等 41 人
Nature Communications
2023
•2023/2/23
•Vol.14 No.1 p.1-21
Mutations in the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial respiration. Within this group, an increasing number of mutations have been identified in nuclear genes involved in mitochondrial RNA biology. The TEFM gen...
Disease geneticsGenetics researchNeurological manifestationsNeuromuscular diseasePathology
10.1038/S41467-023-36277-7
ISSN:2041-1723
Structure and inhibition mechanism of the catalytic domain of human squalene epoxidase
Anil K. Padyana•Stefan Gross•Lei Jin•Giovanni Cianchetta•Rohini Narayanaswamy等 17 人
Nature Communications
2019
•2019/1/9
•Vol.10 No.1 p.1-10
Squalene epoxidase (SQLE), also known as squalene monooxygenase, catalyzes the stereospecific conversion of squalene to 2,3(S)-oxidosqualene, a key step in cholesterol biosynthesis. SQLE inhibition is targeted for the treatment of hypercholesteremia, cancer, and fungal infections. However, lack of s...
CancerChemical toolsEnzyme mechanismsStructure-based drug designX-ray crystallography
10.1038/S41467-018-07928-X
ISSN:2041-1723
Pseudokinases can catalyse peptide cyclization through thioether crosslinking
Ling Hu•Miao Li•Yueqian Sang•Chengxin Zhao•Jiwu Huang等 13 人
Nature Chemistry
2025
•2025/10/2
•00 p.1-12
The protein-kinase-like superfamily proteins are crucial and generally catalyse substrate phosphorylation using adenosine 5′-triphosphate. Pseudokinases are non-canonical protein-kinase-like members deficient in kinase activity, and few of them are known to be enzymatically active and to have cataly...
BiosynthesisEnzyme mechanisms
10.1038/S41557-025-01954-1
ISSN:1755-4330
Molecular basis for the regulation of human phosphorylase kinase by phosphorylation and Ca2+
Ruifang Ma•Bowen Du•Chen Shi•Lei Wang•Fuxing Zeng等 9 人
Nature Communications
2025
•2025/3/28
•Vol.16 No.1 p.1-13
Phosphorylase kinase (PhK) regulates the degradation of glycogen by integrating diverse signals, providing energy to the organism. Dysfunctional mutations may directly lead to Glycogen Storage Disease type IX (GSD IX), whereas the abnormal expression of PhK is also associated with tumors. Here, we u...
Cryoelectron microscopyEnzyme mechanismsKinases
10.1038/S41467-025-58363-8
ISSN:2041-1723
Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy
Liguo Wang•Xuejing Shao•Tianbai Zhong•Yue Wu•Aixiao Xu等 21 人
Nature Chemical Biology
2021
•2021/3/4
•00 p.1-9
The discovery of effective therapeutic treatments for cancer via cell differentiation instead of antiproliferation remains a great challenge. Cyclin-dependent kinase 2 (CDK2) inactivation, which overcomes the differentiation arrest of acute myeloid leukemia (AML) cells, may be a promising method for...
Cancer therapyKinasesMedicinal chemistrySmall molecules
10.1038/S41589-021-00742-5
ISSN:1552-4450
Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit
Molina-Granada David•González-Vioque Emiliano•Dibley Marris G.•Cabrera-Pérez Raquel•Vallbona-Garcia Antoni等 10 人
Communications Biology
2022
•2022/6/23
•Vol.5 No.1 p.1-16
Imbalanced mitochondrial dNTP pools are known players in the pathogenesis of multiple human diseases. Here we show that, even under physiological conditions, dGTP is largely overrepresented among other dNTPs in mitochondria of mouse tissues and human cultured cells. In addition, a vast majority of m...
BiochemistryMolecular medicine
10.1038/S42003-022-03568-6
ISSN:2399-3642
Towards glycan foldamers and programmable assemblies
Surusch Djalali•Nishu Yadav•Martina Delbianco
Nature Reviews Materials
2024
•2024/2/5
•00 p.1-12
Natural biopolymers have inspired the development of synthetic analogues that can adopt defined conformations and assemble into 3D architectures. These compounds are mainly based on peptides and nucleic acids, which are well understood at the molecular level and can be rationally synthesized to obta...
Analytical chemistryCarbohydrate chemistrySupramolecular chemistry
10.1038/S41578-023-00638-X
ISSN:2058-8437
Expanding PROTACtable genome universe of E3 ligases
Yuan Liu•Jingwen Yang•Tianlu Wang•Mei Luo•Yamei Chen等 10 人
Nature Communications
2023
•2023/10/16
•Vol.14 No.1 p.1-17
Proteolysis-targeting chimera (PROTAC) and other targeted protein degradation (TPD) molecules that induce degradation by the ubiquitin-proteasome system (UPS) offer new opportunities to engage targets that remain challenging to be inhibited by conventional small molecules. One fundamental element in...
Cancer genomicsComputational biology and bioinformaticsUbiquitin ligases
10.1038/S41467-023-42233-2
ISSN:2041-1723
Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis
Lie Wang•Ming Zhou
Nature Communications
2023
•2023/5/13
•Vol.14 No.1 p.1-8
Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic cell membranes. In eukaryotes, two highly homologous enzymes, cholinephosphotransferase-1 (CHPT1) and choline/ethanolamine phosphotransferase-1 (CEPT1) catalyze the final step of de novo PC synthesis. CHPT1/CEPT1 joins two subs...
Cryoelectron microscopyPhospholipidsTransferases
10.1038/S41467-023-38003-9
ISSN:2041-1723
Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model
Elizabeth Spangenberg•Paul L. Severson•Lindsay A. Hohsfield•Joshua Crapser•Jiazhong Zhang等 22 人
Nature Communications
2019
•2019/8/21
•Vol.10 No.1 p.1-21
Many risk genes for the development of Alzheimer’s disease (AD) are exclusively or highly expressed in myeloid cells. Microglia are dependent on colony-stimulating factor 1 receptor (CSF1R) signaling for their survival. We designed and synthesized a highly selective brain-penetrant CSF1R inhibitor (...
Alzheimer's diseaseMicroglia
10.1038/S41467-019-11674-Z
ISSN:2041-1723
Revealing reaction intermediates in one-carbon elongation by thiamine diphosphate/CoA-dependent enzyme family
Youngchang Kim•Seung Hwan Lee•Priyanka Gade•Maren Nattermann•Natalia Maltseva等 15 人
Communications Chemistry
2024
•2024/7/21
•Vol.7 No.1 p.1-10
2-Hydroxyacyl-CoA lyase/synthase (HACL/S) is a thiamine diphosphate (ThDP)-dependent versatile enzyme originally discovered in the mammalian α-oxidation pathway. HACL/S natively cleaves 2-hydroxyacyl-CoAs and, in its reverse direction, condenses formyl-CoA with aldehydes or ketones. The one-carbon e...
BiocatalysisEnzyme mechanismsX-ray crystallography
10.1038/S42004-024-01242-Y
ISSN:2399-3669
Structural basis for DNA proofreading
Gina Buchel•Ashok R. Nayak•Karl Herbine•Azadeh Sarfallah•Viktoriia O. Sokolova等 7 人
Nature Communications
2023
•2023/12/27
•Vol.14 No.1 p.1-12
DNA polymerase (DNAP) can correct errors in DNA during replication by proofreading, a process critical for cell viability. However, the mechanism by which an erroneously incorporated base translocates from the polymerase to the exonuclease site and the corrected DNA terminus returns has remained elu...
Cryoelectron microscopyDNADNA synthesis
10.1038/S41467-023-44198-8
ISSN:2041-1723
Nucleoid remodeling during environmental adaptation is regulated by HU-dependent DNA bundling
Soumya G. Remesh•Subhash C. Verma•Jian-Hua Chen•Axel A. Ekman•Carolyn A. Larabell等 7 人
Nature Communications
2020
•2020/6/9
•Vol.11 No.1 p.1-12
Bacterial nucleoid remodeling dependent on conserved histone-like protein, HU is one of the determining factors in global gene regulation. By imaging of near-native, unlabeled E. coli cells by soft X-ray tomography, we show that HU remodels nucleoids by promoting the formation of a dense condensed c...
Bacterial structural biologyDNASAXSX-ray crystallographyX-ray tomography
10.1038/S41467-020-16724-5
ISSN:2041-1723
Photoinduced chemomimetic biocatalysis for enantioselective intermolecular radical conjugate addition
Huang Xiaoqiang•Feng Jianqiang•Cui Jiawen•Jiang Guangde•Harrison Wesley等 9 人
Nature Catalysis
2022
•2022/5/2
•00 p.1-8
Exploiting nature’s catalysts for non-natural transformations that are inaccessible to chemocatalysis is highly desirable but challenging. On the one hand, the widespread nicotinamide-dependent oxidoreductases have not been utilized for single-electron-transfer-induced bimolecular cross-couplings; o...
BiocatalysisEnzyme mechanismsOxidoreductasesProtein designX-ray crystallography
10.1038/S41929-022-00777-4
ISSN:2520-1158
Highly accurate carbohydrate-binding site prediction with DeepGlycanSite
Xinheng He•Lifen Zhao•Yinping Tian•Rui Li•Qinyu Chu等 14 人
Nature Communications
2024
•2024/6/17
•Vol.15 No.1 p.1-13
As the most abundant organic substances in nature, carbohydrates are essential for life. Understanding how carbohydrates regulate proteins in the physiological and pathological processes presents opportunities to address crucial biological problems and develop new therapeutics. However, the diversit...
CarbohydratesMachine learning
10.1038/S41467-024-49516-2
ISSN:2041-1723
Bacterial Hachiman complex executes DNA cleavage for antiphage defense
Yongqing Cui•Zhikang Dai•Yufei Ouyang•Chunyang Fu•Yanjing Wang等 12 人
Nature Communications
2025
•2025/3/17
•Vol.16 No.1 p.1-12
Bacteria have developed a variety of immune systems to combat phage infections. The Hachiman system is a novel prokaryotic antiphage defense system comprising HamA and HamB proteins, which contains the DUF1837 and helicase domains, respectively. However, the defense mechanism remains only partially ...
BacteriophagesCryoelectron microscopy
10.1038/S41467-025-57851-1
ISSN:2041-1723
Exploring protein hotspots by optimized fragment pharmacophores
Dávid Bajusz•Warren S. Wade•Grzegorz Satała•Andrzej J. Bojarski•Janez Ilaš等 19 人
Nature Communications
2021
•2021/5/27
•Vol.12 No.1 p.1-10
Fragment-based drug design has introduced a bottom-up process for drug development, with improved sampling of chemical space and increased effectiveness in early drug discovery. Here, we combine the use of pharmacophores, the most general concept of representing drug-target interactions with the the...
Chemical librariesDrug discovery and development
10.1038/S41467-021-23443-Y
ISSN:2041-1723
Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant
Tomokazu Tamura•Takashi Irie•Sayaka Deguchi•Hisano Yajima•Masumi Tsuda等 38 人
Nature Communications
2024
•2024/2/8
•Vol.15 No.1 p.1-17
Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the S486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays...
Cryoelectron microscopySARS-CoV-2Virus–host interactions
10.1038/S41467-024-45274-3
ISSN:2041-1723
Structural basis for substrate binding and selection by human mitochondrial RNA polymerase
Karl Herbine•Ashok R. Nayak•Dmitry Temiakov
Nature Communications
2024
•2024/8/20
•Vol.15 No.1 p.1-9
The mechanism by which RNAP selects cognate substrates and discriminates between deoxy and ribonucleotides is of fundamental importance to the fidelity of transcription. Here, we present cryo-EM structures of human mitochondrial transcription elongation complexes that reveal substrate ATP bound in E...
Cryoelectron microscopyDNA-binding proteinsTranscription
10.1038/S41467-024-50817-9
ISSN:2041-1723
TGFβ-Smad3 signaling restores cell-autonomous Srsf1-mediated splicing of fibronectin in aged skeletal muscle stem cells
Yuguo Liu•Svenja C. Schüler•Simon Dumontier•Frederic Balg•Sonia Bedard等 9 人
Nature Communications
2025
•2025/11/21
0Loss of Fibronectin (FN) from the skeletal muscle stem cell (MuSC) niche represents a root cause of regenerative failure in aging. While FN has pleiotropic functions during healthy skeletal muscle regeneration, it remains unclear how aging affects its spatiotemporal specificity for MuSCs. Here, we d...
AgeingMuscle stem cellsStem-cell niche
10.1038/S41467-025-66582-2
ISSN:2041-1723
Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO
Andrea de la Fuente-Alonso•Marta Toral•Alvaro Alfayate•María Jesús Ruiz-Rodríguez•Elena Bonzón-Kulichenko等 21 人
Nature Communications
2021
•2021/5/11
•Vol.12 No.1 p.1-18
Thoracic aortic aneurysm, as occurs in Marfan syndrome, is generally asymptomatic until dissection or rupture, requiring surgical intervention as the only available treatment. Here, we show that nitric oxide (NO) signaling dysregulates actin cytoskeleton dynamics in Marfan Syndrome smooth muscle cel...
AneurysmAortic diseases
10.1038/S41467-021-22933-3
ISSN:2041-1723
Drug repurposing screen identifies lonafarnib as respiratory syncytial virus fusion protein inhibitor
Svenja M. Sake•Xiaoyu Zhang•Manoj Kumar Rajak•Melanie Urbanek-Quaing•Arnaud Carpentier等 32 人
Nature Communications
2024
•2024/2/8
•Vol.15 No.1 p.1-15
Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infection in infants, older adults and the immunocompromised. Effective directly acting antivirals are not yet available for clinical use. To address this, we screen the ReFRAME drug-repurposing library consisting o...
AntiviralsHigh-throughput screeningMouse
10.1038/S41467-024-45241-Y
ISSN:2041-1723
Cryo-EM reveals evolutionarily conserved and distinct structural features of plant CG maintenance methyltransferase MET1
Amika Kikuchi•Atsuya Nishiyama•Yoshie Chiba•Makoto Nakanishi•Taiko Kim To等 6 人
Nature Communications
2025
•2025/9/26
•Vol.16 No.1 p.1-15
DNA methylation is essential for genomic function and transposable element silencing. In plants, DNA methylation occurs in CG, CHG, and CHH contexts (where H = A, T, or C), with the maintenance of CG methylation mediated by the DNA methyltransferase MET1. The molecular mechanism by which MET1 mainta...
Cryoelectron microscopyDNA methylationEnzyme mechanismsPlant molecular biology
10.1038/S41467-025-63765-9
ISSN:2041-1723
Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism
Magdalena Kremer•Sabrina Schulze•Nadja Eisenbruch•Felix Nagel•Robert Vogt等 16 人
Nature Communications
2024
•2024/2/23
•Vol.15 No.1 p.1-25
The Escherichia coli TetR-related transcriptional regulator RutR is involved in the coordination of pyrimidine and purine metabolism. Here we report that lysine acetylation modulates RutR function. Applying the genetic code expansion concept, we produced site-specifically lysine-acetylated RutR prot...
Bacterial transcriptionTranscriptionX-ray crystallography
10.1038/S41467-024-46039-8
ISSN:2041-1723
Structural analysis of an anthrol reductase inspires enantioselective synthesis of enantiopure hydroxycycloketones and β-halohydrins
Hou Xiaodong•Xu Huibin•Yuan Zhenbo•Deng Zhiwei•Fu Kai等 9 人
Nature Communications
2023
•2023/1/21
•Vol.14 No.1 p.1-10
Asymmetric reduction of prochiral ketones, particularly, reductive desymmetrization of 2,2-disubstituted prochiral 1,3-cyclodiketones to produce enantiopure chiral alcohols is challenging. Herein, an anthrol reductase CbAR with the ability to accommodate diverse bulky substrates, like emodin, for as...
BiocatalysisEnzyme mechanismsSmall molecules
10.1038/S41467-023-36064-4
ISSN:2041-1723
Solution structure of recombinant Pvfp-5β reveals insights into mussel adhesion
Morando Maria Agnese•Venturella Francesca•Sollazzo Martina•Monaca Elisa•Sabbatella Raffaele等 9 人
Communications Biology
2022
•2022/7/25
•Vol.5 No.1 p.1-10
Some marine organisms can resist to aqueous tidal environments and adhere tightly on wet surface. This behavior has raised increasing attention for potential applications in medicine, biomaterials, and tissue engineering. In mussels, adhesive forces to the rock are the resultant of proteinic fibrous...
Solution-state NMRTranslational research
10.1038/S42003-022-03699-W
ISSN:2399-3642
Structural insights into the molecular mechanisms of OsFBN5-induced OsSPS3 catalysis
Han Xiao•Xing-Xing Shi•Min Li•You-Wang Wang•Da-Wei Wang等 9 人
Nature Plants
2026
•2026/1/5
•Vol.12 No.1 p.217-230
Solanesyl diphosphate synthase (SPS) is crucial for photosynthesis, as it supplies prenyl precursors for the biosynthesis of the photosynthetic electron carrier, plastoquinone-9 (PQ-9). Fibrillin 5 (FBN5) stimulates SPS catalytic activity through direct binding, which is essential for normal plant g...
PhotosynthesisPlant molecular biology
10.1038/S41477-025-02184-6
ISSN:2055-0278
In vivo clonal expansion and phenotypes of hypocretin-specific CD4 + T cells in narcolepsy patients and controls
Wei Jiang•James R. Birtley•Shu-Chen Hung•Weiqi Wang•Shin-Heng Chiou等 18 人
Nature Communications
2019
•2019/11/20
•Vol.10 No.1 p.1-17
Individuals with narcolepsy suffer from abnormal sleep patterns due to loss of neurons that uniquely supply hypocretin (HCRT). Previous studies found associations of narcolepsy with the human leukocyte antigen (HLA)-DQ6 allele and T-cell receptor α (TRA) J24 gene segment and also suggested that in v...
Autoimmune diseasesNeuroimmunologyPeripheral toleranceSleep disordersT-cell receptor
10.1038/S41467-019-13234-X
ISSN:2041-1723
SIgA structures bound to Streptococcus pyogenes M4 and human CD89 provide insights into host-pathogen interactions
Qianqiao Liu•Beth M. Stadtmueller
Nature Communications
2023
•2023/10/23
•Vol.14 No.1 p.1-12
Immunoglobulin (Ig) A functions as monomeric IgA in the serum and Secretory (S) IgA in mucosal secretions. Host IgA Fc receptors (FcαRs), including human FcαR1/CD89, mediate IgA effector functions; however, human pathogen Streptococcus pyogenes has evolved surface-protein virulence factors, includin...
Adaptive immunityAntimicrobial responsesBacterial immune evasionCryoelectron microscopyMucosal immunology
10.1038/S41467-023-42469-Y
ISSN:2041-1723
Ab initio characterization of protein molecular dynamics with AI2BMD
Tong Wang•Xinheng He•Mingyu Li•Yatao Li•Ran Bi等 15 人
Nature
2024
•2024/11/6
•00 p.1-9
Biomolecular dynamics simulation is a fundamental technology for life sciences research, and its usefulness depends on its accuracy and efficiency1–3. Classical molecular dynamics simulation is fast but lacks chemical accuracy4,5. Quantum chemistry methods such as density functional theory can reach...
Computational biology and bioinformaticsStructural biology
10.1038/S41586-024-08127-Z
ISSN:0028-0836
Hierarchical graph learning for protein–protein interaction
Gao Ziqi•Jiang Chenran•Zhang Jiawen•Jiang Xiaosen•Li Lanqing等 9 人
Nature Communications
2023
•2023/2/25
•Vol.14 No.1 p.1-12
Protein-Protein Interactions (PPIs) are fundamental means of functions and signalings in biological systems. The massive growth in demand and cost associated with experimental PPI studies calls for computational tools for automated prediction and understanding of PPIs. Despite recent progress, in si...
Machine learningProteome informatics
10.1038/S41467-023-36736-1
ISSN:2041-1723
Snapshots and ensembles of BTK and cIAP1 protein degrader ternary complexes
James Schiemer•Reto Horst•Yilin Meng•Justin I. Montgomery•Yingrong Xu等 16 人
Nature Chemical Biology
2020
•2020/11/16
•Vol.17 No.2 p.152-160
Heterobifunctional chimeric degraders are a class of ligands that recruit target proteins to E3 ubiquitin ligases to drive compound-dependent protein degradation. Advancing from initial chemical tools, protein degraders represent a mechanism of growing interest in drug discovery. Critical to the mec...
Mechanism of actionSmall moleculesStructural biology
10.1038/S41589-020-00686-2
ISSN:1552-4450
ClickGen: Directed exploration of synthesizable chemical space via modular reactions and reinforcement learning
Mingyang Wang•Shuai Li•Jike Wang•Odin Zhang•Hongyan Du等 15 人
Nature Communications
2024
•2024/11/22
•Vol.15 No.1 p.1-18
Despite the significant potential of generative models, low synthesizability of many generated molecules limits their real-world applications. In response to this issue, we develop ClickGen, a deep learning model that utilizes modular reactions like click chemistry to assemble molecules and incorpor...
CheminformaticsMachine learningVirtual screening
10.1038/S41467-024-54456-Y
ISSN:2041-1723
A scalable reinforcement learning approach for screening large peptide libraries for bioactive peptide discovery
Mohit Pandey•Jane Foo•Shabnam Massah•Morgan A. Alford•Hazem Mslati等 13 人
Nature Communications
2025
•2025/11/27
0Bioactive peptides such as anticancer peptides (ACPs) offer a promising therapeutic alternative to small molecules due to their efficiency and selectivity against tumors and minimal toxicity towards healthy human cells. However, their rational discovery requires navigating a vast chemical space usin...
Drug discoveryMachine learningVirtual drug screening
10.1038/S41467-025-66748-Y
ISSN:2041-1723
DIP-MS: ultra-deep interaction proteomics for the deconvolution of protein complexes
Fabian Frommelt•Andrea Fossati•Federico Uliana•Fabian Wendt•Peng Xue等 10 人
Nature Methods
2024
•2024/3/26
•00 p.1-13
Most proteins are organized in macromolecular assemblies, which represent key functional units regulating and catalyzing most cellular processes. Affinity purification of the protein of interest combined with liquid chromatography coupled to tandem mass spectrometry (AP–MS) represents the method of ...
Protein–protein interaction networksProteomic analysisSoftware
10.1038/S41592-024-02211-Y
ISSN:1548-7091
Direct binding of TFEα opens DNA binding cleft of RNA polymerase
Sung-Hoon Jun•Jaekyung Hyun•Jeong Seok Cha•Hoyoung Kim•Michael S. Bartlett等 7 人
Nature Communications
2020
•2020/11/30
•Vol.11 No.1 p.1-12
Opening of the DNA binding cleft of cellular RNA polymerase (RNAP) is necessary for transcription initiation but the underlying molecular mechanism is not known. Here, we report on the cryo-electron microscopy structures of the RNAP, RNAP-TFEα binary, and RNAP-TFEα-promoter DNA ternary complexes fro...
Cryoelectron microscopyEnzyme mechanismsRNATranscriptionX-ray crystallography
10.1038/S41467-020-19998-X
ISSN:2041-1723
Bioengineered ferritin-based lysosome-targeting chimera platform for tumor-targeted therapy
Shuai Zhang•Yiliang Jin•Yaxin Hou•Guoheng Tang•Zhuoran Wang等 8 人
Nature Communications
2026
•2026/3/9
0Lysosome-targeting chimeras (LYTACs) hold therapeutic potential by degrading pathogenesis-associated proteins. However, current LYTAC systems often require considerable effort for case-by-case construction and are devoid of a convenient and efficient modular platform. Here, we develop a modular LYTA...
Biomaterials – proteinsNanotechnology in cancerTargeted therapies
10.1038/S41467-026-70383-6
ISSN:2041-1723
Structural and virological identification of neutralizing antibody footprint provides insights into therapeutic antibody design against SARS-CoV-2 variants
Yuki Anraku•Shunsuke Kita•Taishi Onodera•Akihiko Sato•Takashi Tadokoro等 25 人
Communications Biology
2025
•2025/3/22
•Vol.8 No.1 p.1-12
Medical treatments using potent neutralizing SARS-CoV-2 antibodies have achieved remarkable improvements in clinical symptoms, changing the situation for the severity of COVID-19 patients. We previously reported an antibody, NT-108 with potent neutralizing activity. However, the structural and funct...
Antibody fragment therapyCryoelectron microscopySARS-CoV-2X-ray crystallography
10.1038/S42003-025-07827-0
ISSN:2399-3642
Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate
Elena Ethel Vidal-Calvo•Anne Martin-Salazar•Swati Choudhary•Robert Dagil•Sai Sundar Rajan Raghavan等 41 人
Nature Communications
2024
•2024/8/30
•Vol.15 No.1 p.1-20
Molecular similarities between embryonic and malignant cells can be exploited to target tumors through specific signatures absent in healthy adult tissues. One such embryonic signature tumors express is oncofetal chondroitin sulfate (ofCS), which supports disease progression and dissemination in can...
Cancer imagingCancer microenvironmentMolecular medicineTargeted therapiesTumour biomarkers
10.1038/S41467-024-51781-0
ISSN:2041-1723
Data-mining unveils structure–property–activity correlation of viral infectivity enhancing self-assembling peptides
Kübra Kaygisiz•Lena Rauch-Wirth•Arghya Dutta•Xiaoqing Yu•Yuki Nagata等 9 人
Nature Communications
2023
•2023/8/23
•Vol.14 No.1 p.1-17
Gene therapy via retroviral vectors holds great promise for treating a variety of serious diseases. It requires the use of additives to boost infectivity. Amyloid-like peptide nanofibers (PNFs) were shown to efficiently enhance retroviral gene transfer. However, the underlying mode of action of thes...
Biomedical materialsData miningMolecular self-assemblyPeptidesSelf-assembly
10.1038/S41467-023-40663-6
ISSN:2041-1723
Structural anatomy of Protein Kinase C C1 domain interactions with diacylglycerol and other agonists
Katti Sachin S.•Krieger Inna V.•Ann Jihyae•Lee Jeewoo•Sacchettini James C.等 6 人
Nature Communications
2022
•2022/5/16
•Vol.13 No.1 p.1-11
Diacylglycerol (DAG) is a versatile lipid whose 1,2-sn-stereoisomer serves both as second messenger in signal transduction pathways that control vital cellular processes, and as metabolic precursor for downstream signaling lipids such as phosphatidic acid. Effector proteins translocate to available ...
Biophysical chemistryKinasesMembrane biophysicsMolecular conformation
10.1038/S41467-022-30389-2
ISSN:2041-1723
A Rieske oxygenase/epoxide hydrolase-catalysed reaction cascade creates oxygen heterocycles in mupirocin biosynthesis
Luoyi Wang•Alice Parnell•Christopher Williams•Nurfarhanim A. Bakar•Martin R. Challand等 10 人
Nature Catalysis
2018
•2018/11/26
•Vol.1 No.12 p.968-976
Oxygen heterocycles—in particular, tetrahydropyrans (THPs) and tetrahydrofurans—are common structural features of many biologically active polyketide natural products. Mupirocin is a clinically important antibiotic isolated from Pseudomonas fluorescens and is assembled on a THP ring, which is essent...
AntibioticsBiosynthesisHydrolasesNatural productsOxidoreductases
10.1038/S41929-018-0183-5
ISSN:2520-1158
FBXO7, a tumor suppressor in endometrial carcinoma, suppresses INF2-associated mitochondrial division
Hui Zhang•Yiting Zhao•Jie Wang•Jinyun Li•Jingyi Xia等 13 人
Cell Death & Disease
2023
•2023/6/21
•Vol.14 No.6 p.1-16
Endometrial carcinoma (ECa) is the most common malignant gynecological cancer, with an increased incidence and fatality rate worldwide, while the pathogenesis is still largely unknown. In this study, we confirmed that FBXO7, a gene coding FBXO7 E3 ubiquitin ligase, is significantly downregulated and...
Cancer geneticsOncogenes
10.1038/S41419-023-05891-0
ISSN:2041-4889
A glyoxal-specific aldehyde signaling axis in Pseudomonas aeruginosa that influences quorum sensing and infection
Christopher J. Corcoran•Bonnie J. Cuthbert•David G. Glanville•Mailyn Terrado•Diana Valverde Mendez等 24 人
Nature Communications
2025
•2025/7/18
•Vol.16 No.1 p.1-24
The universally conserved α-oxoaldehydes glyoxal (GO) and methylglyoxal (MGO) are toxic metabolic byproducts whose accumulation can lead to cell death. In the absence of a known, natural inducer of the GO-specific response in prokaryotes, we exploited RNA-seq to define a GO response in the bacterial...
Bacterial pathogenesisBacteriologyInfection
10.1038/S41467-025-61469-8
ISSN:2041-1723
A dual role in regulation and toxicity for the disordered N-terminus of the toxin GraT
Ariel Talavera•Hedvig Tamman•Andres Ainelo•Albert Konijnenberg•San Hadži等 9 人
Nature Communications
2019
•2019/2/27
•Vol.10 No.1 p.1-13
Bacterial toxin-antitoxin (TA) modules are tightly regulated to maintain growth in favorable conditions or growth arrest during stress. A typical regulatory strategy involves the antitoxin binding and repressing its own promoter while the toxin often acts as a co-repressor. Here we show that Pseudom...
DNA-binding proteinsIntrinsically disordered proteinsMicrobiologyProteinsX-ray crystallography
10.1038/S41467-019-08865-Z
ISSN:2041-1723
Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood
Mathias Jensen•Linn Stenfelt•Jennifer Ricci Hagman•Michael Jakob Pichler•Julia Weikum等 10 人
Nature Microbiology
2024
•2024/4/29
•00 p.1-13
Matching donor and recipient blood groups based on red blood cell (RBC) surface ABO glycans and antibodies in plasma is crucial to avoid potentially fatal reactions during transfusions. Enzymatic conversion of RBC glycans to the universal group O is an attractive solution to simplify blood logistics...
Applied immunologyBiocatalysis
10.1038/S41564-024-01663-4
ISSN:2058-5276
Covalent binding of uracil DNA glycosylase UdgX to abasic DNA upon uracil excision
Woo-Chan Ahn•Shashanka Aroli•Jin-Hahn Kim•Jeong Hee Moon•Ga Seal Lee等 10 人
Nature Chemical Biology
2019
•2019/5/17
•Vol.15 No.6 p.607-614
Uracil DNA glycosylases (UDGs) are important DNA repair enzymes that excise uracil from DNA, yielding an abasic site. Recently, UdgX, an unconventional UDG with extremely tight binding to DNA containing uracil, was discovered. The structure of UdgX from Mycobacterium smegmatis in complex with DNA sh...
DNAEnzyme mechanismsEnzymesX-ray crystallography
10.1038/S41589-019-0289-3
ISSN:1552-4450
An enzymatic Alder-ene reaction
Masao Ohashi•Cooper S. Jamieson•Yujuan Cai•Dan Tan•Daiki Kanayama等 16 人
Nature
2020
•2020/9/30
•Vol.586 No.7827 p.64-69
An ongoing challenge in chemical research is to design catalysts that select the outcomes of the reactions of complex molecules. Chemists rely on organocatalysts or transition metal catalysts to control stereoselectivity, regioselectivity and periselectivity (selectivity among possible pericyclic re...
BiosynthesisEnzyme mechanismsNatural products
10.1038/S41586-020-2743-5
ISSN:0028-0836
A conformational switch controlling the toxicity of the prion protein
Frontzek Karl•Bardelli Marco•Senatore Assunta•Henzi Anna•Reimann Regina R.等 24 人
Nature Structural & Molecular Biology
2022
•2022/8/10
•Vol.29 No.8 p.831-840
Prion infections cause conformational changes of the cellular prion protein (PrPC) and lead to progressive neurological impairment. Here we show that toxic, prion-mimetic ligands induce an intramolecular R208-H140 hydrogen bond (‘H-latch’), altering the flexibility of the α2–α3 and β2–α2 loops of Pr...
Molecular modellingPrions
10.1038/S41594-022-00814-7
ISSN:1545-9993
Analysis of heterocycle formation and stereochemical control by a non-ribosomal peptide synthetase condensation domain
Wei Cao•Jialiang Wang•Shyue Leh Chen•Dandan Li•Xiaozheng Wang等 8 人
Nature Synthesis
2026
•2026/3/23
•00 p.1-16
Non-ribosomal peptide synthetases (NRPSs) produce diverse bioactive peptides, including antibiotics and antitumour agents, by integrating proteinogenic and non-proteinogenic amino acids alongside tailoring modifications, such as epimerization (E) and cyclization. Here we demonstrate that the tetrahy...
BiocatalysisCryoelectron microscopySynthetic biology
10.1038/S44160-026-01014-7
ISSN:2731-0582
Binding mode of Isoxazolyl Penicillins to a Class-A β-lactamase at ambient conditions
Gargi Gore•Andreas Prester•David von Stetten•Kim Bartels•Eike C. Schulz
Communications Chemistry
2025
•2025/12/1
•Vol.8 No.1 p.3870
The predominant resistance mechanism observed in Gram-negative bacteria involves the production of β-lactamases, which catalyse the hydrolysis of β-lactam antibiotics, thereby rendering them ineffective. Although Isoxazolyl Penicillins have been available since the 1970s, there are currently no stru...
Drug discoveryX-ray crystallography
10.1038/S42004-025-01801-X
ISSN:2399-3669
Multivalent bicyclic peptides are an effective antiviral modality that can potently inhibit SARS-CoV-2
Katherine U. Gaynor•Marina Vaysburd•Maximilian A. J. Harman•Anna Albecka•Phillip Jeffrey等 32 人
Nature Communications
2023
•2023/6/16
•Vol.14 No.1 p.1-15
COVID-19 has stimulated the rapid development of new antibody and small molecule therapeutics to inhibit SARS-CoV-2 infection. Here we describe a third antiviral modality that combines the drug-like advantages of both. Bicycles are entropically constrained peptides stabilized by a central chemical s...
Antiviral agentsPharmaceuticsSARS-CoV-2Viral infection
10.1038/S41467-023-39158-1
ISSN:2041-1723
Transient disome complex formation in native polysomes during ongoing protein synthesis captured by cryo-EM
Timo Flügel•Magdalena Schacherl•Anett Unbehaun•Birgit Schroeer•Marylena Dabrowski等 11 人
Nature Communications
2024
•2024/2/26
•Vol.15 No.1 p.1-15
Structural studies of translating ribosomes traditionally rely on in vitro assembly and stalling of ribosomes in defined states. To comprehensively visualize bacterial translation, we reactivated ex vivo-derived E. coli polysomes in the PURE in vitro translation system and analyzed the actively elon...
Cryoelectron microscopyRibosome
10.1038/S41467-024-46092-3
ISSN:2041-1723
Computational design of bifaceted protein nanomaterials
Sanela Rankovic•Kenneth D. Carr•Justin Decarreau•Rebecca Skotheim•Ryan D. Kibler等 16 人
Nature Materials
2025
•2025/7/31
•00 p.1-9
Advances in computational methods have led to considerable progress in the design of protein nanomaterials. However, nearly all nanoparticles designed so far exhibit strict point group symmetry, which limits structural diversity and precludes anisotropic functionalization. Here we describe a computa...
Electron microscopyNanoparticlesNanostructuresProtein designProteins
10.1038/S41563-025-02295-7
ISSN:1476-1122
CryoREAD: de novo structure modeling for nucleic acids in cryo-EM maps using deep learning
Xiao Wang•Genki Terashi•Daisuke Kihara
Nature Methods
2023
•2023/10/2
•00 p.1-9
DNA and RNA play fundamental roles in various cellular processes, where their three-dimensional structures provide information critical to understanding the molecular mechanisms of their functions. Although an increasing number of nucleic acid structures and their complexes with proteins are determi...
Cryoelectron microscopyMachine learningRNASoftware
10.1038/S41592-023-02032-5
ISSN:1548-7091
Single-sequence protein structure prediction using supervised transformer protein language models
Wang Wenkai•Peng Zhenling•Yang Jianyi
Nature Computational Science
2022
•2022/12/19
•Vol.2 No.12 p.804-814
Significant progress has been made in protein structure prediction in recent years. However, it remains challenging for AlphaFold2 and other deep learning-based methods to predict protein structure with single-sequence input. Here we introduce trRosettaX-Single, an automated algorithm for single-seq...
Machine learningProtein structure predictions
10.1038/S43588-022-00373-3
ISSN:2662-8457
Infectious parvovirus B19 circulates in the blood coated with active host protease inhibitors
Hyunwook Lee•Ruben Assaraf•Suriyasri Subramanian•Dan Goetschius•Jan Bieri等 10 人
Nature Communications
2024
•2024/11/5
•Vol.15 No.1 p.1-15
The lack of a permissive cell culture system has limited high-resolution structures of parvovirus B19 (B19V) to virus-like particles (VLPs). In this study, we present the atomic resolution structure (2.2 Å) of authentic B19V purified from a patient blood sample. There are significant differences com...
Cryoelectron microscopyVirology
10.1038/S41467-024-53794-1
ISSN:2041-1723
The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation
Meier Markus•Gupta Monika•Akgül Serife•McDougall Matthew•Imhof Thomas等 20 人
Nature Communications
2023
•2023/3/3
•Vol.14 No.1 p.1-18
Netrin-1 is a bifunctional chemotropic guidance cue that plays key roles in diverse cellular processes including axon pathfinding, cell migration, adhesion, differentiation, and survival. Here, we present a molecular understanding of netrin-1 mediated interactions with glycosaminoglycan chains ...
Biophysical chemistryCaenorhabditis elegansIntracellular signalling peptides and proteinsX-ray crystallography
10.1038/S41467-023-36692-W
ISSN:2041-1723
Structural basis of tubulin detyrosination by the vasohibin–SVBP enzyme complex
Na Wang•Christophe Bosc•Sung Ryul Choi•Benoit Boulan•Leticia Peris等 14 人
Nature Structural & Molecular Biology
2019
•2019/6/24
•Vol.26 No.7 p.571-582
Vasohibins are tubulin tyrosine carboxypeptidases that are important in neuron physiology. We examined the crystal structures of human vasohibin 1 and 2 in complex with small vasohibin-binding protein (SVBP) in the absence and presence of different inhibitors and a C-terminal α-tubulin peptide. In c...
ProteasesX-ray crystallography
10.1038/S41594-019-0241-Y
ISSN:1545-9993
Mitochondrial sorting and assembly machinery operates by β-barrel switching
Hironori Takeda•Akihisa Tsutsumi•Tomohiro Nishizawa•Caroline Lindau•Jon V. Busto等 22 人
Nature
2021
•2021/1/6
•Vol.590 No.7844 p.163-169
The mitochondrial outer membrane contains so-called β-barrel proteins, which allow communication between the cytosol and the mitochondrial interior1–3. Insertion of β-barrel proteins into the outer membrane is mediated by the multisubunit mitochondrial sorting and assembly machinery (SAM, also known...
Cryoelectron microscopyMitochondriaProtein translocation
10.1038/S41586-020-03113-7
ISSN:0028-0836
Cryo EM structures map a post vaccination polyclonal antibody response to canine parvovirus
Samantha R. Hartmann•Andrew J. Charnesky•Simon P. Früh•Robert A. López-Astacio•Wendy S. Weichert等 10 人
Communications Biology
2023
•2023/9/19
•Vol.6 No.1 p.1-11
Canine parvovirus (CPV) is an important pathogen that emerged by cross-species transmission to cause severe disease in dogs. To understand the host immune response to vaccination, sera from dogs immunized with parvovirus are obtained, the polyclonal antibodies are purified and used to solve the high...
Cryoelectron microscopyVirus structures
10.1038/S42003-023-05319-7
ISSN:2399-3642
Physicochemical graph neural network for learning protein–ligand interaction fingerprints from sequence data
Huan Yee Koh•Anh T. N. Nguyen•Shirui Pan•Lauren T. May•Geoffrey I. Webb
Nature Machine Intelligence
2024
•2024/6/17
•Vol.6 No.6 p.673-687
In drug discovery, determining the binding affinity and functional effects of small-molecule ligands on proteins is critical. Current computational methods can predict these protein–ligand interaction properties but often lose accuracy without high-resolution protein structures and falter in predict...
Machine learningVirtual screening
10.1038/S42256-024-00847-1
ISSN:2522-5839
Conformational trajectory of allosteric gating of the human cone photoreceptor cyclic nucleotide-gated channel
Zhengshan Hu•Xiangdong Zheng•Jian Yang
Nature Communications
2023
•2023/7/18
•Vol.14 No.1 p.1-16
Cyclic nucleotide-gated (CNG) channels transduce chemical signals into electrical signals in sensory receptors and neurons. They are activated by cGMP or cAMP, which bind to the cyclic nucleotide-binding domain (CNBD) to open a gate located 50-60 Å away in the central cavity. Structures of closed an...
Cryoelectron microscopyCyclic nucleotide-gated cation channels
10.1038/S41467-023-39971-8
ISSN:2041-1723
Catalytic trajectory of a dimeric nonribosomal peptide synthetase subunit with an inserted epimerase domain
Wang Jialiang•Li Dandan•Chen Lu•Cao Wei•Kong Liangliang等 10 人
Nature Communications
2022
•2022/2/1
•Vol.13 No.1 p.1-12
Nonribosomal peptide synthetases (NRPSs) are modular assembly-line megaenzymes that synthesize diverse metabolites with wide-ranging biological activities. The structural dynamics of synthetic elongation has remained unclear. Here, we present cryo-EM structures of PchE, an NRPS elongation module, in...
Cryoelectron microscopyEnzyme mechanisms
10.1038/S41467-022-28284-X
ISSN:2041-1723
Structural basis for the carboxylation and epoxidation of human gamma-glutamyl carboxylase
Wenjie Zhang•Qiaoyue Chen•Bolun Zhang•Hongwu Qian
Nature Communications
2026
•2026/3/27
0Gamma-glutamyl carboxylase (GGCX) is the sole enzyme responsible for gamma carboxylation of glutamate in a vitamin K-dependent manner. This process is crucial for blood coagulation, bone metabolism, vascular calcification, and other biological processes because gamma carboxylation is essential for t...
Cryoelectron microscopyEnzyme mechanismsPost-translational modifications
10.1038/S41467-026-71212-6
ISSN:2041-1723
Inhibition of falcilysin from Plasmodium falciparum by interference with its closed-to-open dynamic transition
Jianqing Lin•Xinfu Yan•Zara Chung•Chong Wai Liew•Abbas El Sahili等 10 人
Communications Biology
2024
•2024/8/31
•Vol.7 No.1 p.1-14
In the absence of an efficacious vaccine, chemotherapy remains crucial to prevent and treat malaria. Given its key role in haemoglobin degradation, falcilysin constitutes an attractive target. Here, we reveal the mechanism of enzymatic inhibition of falcilysin by MK-4815, an investigational new drug...
Cryoelectron microscopyEnzyme mechanismsPathogensProteasesTarget validation
10.1038/S42003-024-06774-6
ISSN:2399-3642
Structural basis for the complex DNA binding behavior of the plant stem cell regulator WUSCHEL
Jeremy Sloan•Jana P. Hakenjos•Michael Gebert•Olga Ermakova•Andrea Gumiero等 9 人
Nature Communications
2020
•2020/5/6
•Vol.11 No.1 p.1-16
Stem cells are one of the foundational evolutionary novelties that allowed the independent emergence of multicellularity in the plant and animal lineages. In plants, the homeodomain (HD) transcription factor WUSCHEL (WUS) is essential for the maintenance of stem cells in the shoot apical meristem. W...
DNA-binding proteinsPlant stem cellTranscriptionX-ray crystallography
10.1038/S41467-020-16024-Y
ISSN:2041-1723
The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes
Erna Davydova•Tadahiro Shimazu•Maren Kirstin Schuhmacher•Magnus E. Jakobsson•Hanneke L. D. M. Willemen等 28 人
Nature Communications
2021
•2021/2/9
•Vol.12 No.1 p.1-14
Post-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is a ...
MethylationProteomicsTransferases
10.1038/S41467-020-20670-7
ISSN:2041-1723
Chemical screening by time-resolved X-ray scattering to discover allosteric probes
Chris A. Brosey•Todd M. Link•Runze Shen•Davide Moiani•Kathryn Burnett等 8 人
Nature Chemical Biology
2024
•2024/4/26
•00 p.1-11
Drug discovery relies on efficient identification of small-molecule leads and their interactions with macromolecular targets. However, understanding how chemotypes impact mechanistically important conformational states often remains secondary among high-throughput discovery methods. Here, we present...
Enzyme mechanismsMedicinal chemistryScreeningSmall moleculesStructural biology
10.1038/S41589-024-01609-1
ISSN:1552-4450
PCRCR complex is essential for invasion of human erythrocytes by Plasmodium falciparum
Scally Stephen W.•Triglia Tony•Evelyn Cindy•Seager Benjamin A.•Pasternak Michał等 13 人
Nature Microbiology
2022
•2022/11/17
•Vol.7 No.12 p.2039-2053
The most severe form of malaria is caused by Plasmodium falciparum. These parasites invade human erythrocytes, and an essential step in this process involves the ligand PfRh5, which forms a complex with cysteine-rich protective antigen (CyRPA) and PfRh5-interacting protein (PfRipr) (RCR complex) and...
Parasite biologyX-ray crystallography
10.1038/S41564-022-01261-2
ISSN:2058-5276
Heme-binding enables allosteric modulation in an ancient TIM-barrel glycosidase
Gloria Gamiz-Arco•Luis I. Gutierrez-Rus•Valeria A. Risso•Beatriz Ibarra-Molero•Yosuke Hoshino等 14 人
Nature Communications
2021
•2021/1/15
•Vol.12 No.1 p.1-16
Glycosidases are phylogenetically widely distributed enzymes that are crucial for the cleavage of glycosidic bonds. Here, we present the exceptional properties of a putative ancestor of bacterial and eukaryotic family-1 glycosidases. The ancestral protein shares the TIM-barrel fold with its modern d...
EnzymesMolecular evolutionProtein designProtein structure predictionsX-ray crystallography
10.1038/S41467-020-20630-1
ISSN:2041-1723
Natural evidence of coronaviral 2′-O-methyltransferase activity affecting viral pathogenesis via improved substrate RNA binding
Jikai Deng•Shimin Yang•Yingjian Li•Xue Tan•Jiejie Liu等 15 人
Signal Transduction And Targeted Therapy
2024
•2024/5/29
•Vol.9 No.1 p.1-16
Previous studies through targeted mutagenesis of K-D-K-E motif have demonstrated that 2′-O-MTase activity is essential for efficient viral replication and immune evasion. However, the K-D-K-E catalytic motif of 2′-O-MTase is highly conserved across numerous viruses, including flaviviruses, vaccinia ...
InflammationMicrobiology
10.1038/S41392-024-01860-X
ISSN:2059-3635
Ciliary central apparatus structure reveals mechanisms of microtubule patterning
Gui Miao•Wang Xiangli•Dutcher Susan K.•Brown Alan•Zhang Rui
Nature Structural & Molecular Biology
2022
•2022/5/16
•Vol.29 No.5 p.483-492
A pair of extensively modified microtubules form the central apparatus (CA) of the axoneme of most motile cilia, where they regulate ciliary motility. The external surfaces of both CA microtubules are patterned asymmetrically with large protein complexes that repeat every 16 or 32 nm. The compositio...
CiliaCryoelectron microscopyMotility
10.1038/S41594-022-00770-2
ISSN:1545-9993
Molecular basis for substrate recognition and transport of human GABA transporter GAT1
Angqi Zhu•Junhao Huang•Fang Kong•Jiaxin Tan•Jianlin Lei等 7 人
Nature Structural & Molecular Biology
2023
•2023/7/3
•00 p.1-11
γ-Aminobutyric acid (GABA), an important inhibitory neurotransmitter in the central nervous system, is recycled through specific GABA transporters (GATs). GAT1, which is mainly expressed in the presynaptic terminals of axons, is a potential drug target of neurological disorders due to its essential ...
BiochemistryCryoelectron microscopy
10.1038/S41594-023-00983-Z
ISSN:1545-9993
Oxidative cleavage of hexopyranose by a TIM-barrel isomerase
Pengwei Li•Dacheng Wang•Lu Guo•Yanru Chen•Huijin Mao等 12 人
Nature Catalysis
2025
•2025/9/24
•00 p.1-13
Cleavage of hexopyranose to short-chain carbohydrates plays crucial roles in carbon metabolism and energy supply. Currently, the carbon–carbon bond scission of hexopyranose involves two types of reaction: the widely distributed retro-aldol reaction and the transketo-like reaction observed in Bifidob...
Enzyme mechanismsMonosaccharides
10.1038/S41929-025-01412-8
ISSN:2520-1158
Alternative splicing controls teneurin-latrophilin interaction and synapse specificity by a shape-shifting mechanism
Jingxian Li•Yuan Xie•Shaleeka Cornelius•Xian Jiang•Richard Sando等 11 人
Nature Communications
2020
•2020/5/1
•Vol.11 No.1 p.1-17
The trans-synaptic interaction of the cell-adhesion molecules teneurins (TENs) with latrophilins (LPHNs/ADGRLs) promotes excitatory synapse formation when LPHNs simultaneously interact with FLRTs. Insertion of a short alternatively-spliced region within TENs abolishes the TEN-LPHN interaction and sw...
Neural circuitsStructural biology
10.1038/S41467-020-16029-7
ISSN:2041-1723
An N-terminal conserved region in human Atg3 couples membrane curvature sensitivity to conjugase activity during autophagy
Yansheng Ye•Erin R. Tyndall•Van Bui•Zhenyuan Tang•Yan Shen等 9 人
Nature Communications
2021
•2021/1/14
•Vol.12 No.1 p.1-11
During autophagy the enzyme Atg3 catalyzes the covalent conjugation of LC3 to the amino group of phosphatidylethanolamine (PE) lipids, which is one of the key steps in autophagosome formation. Here, we have demonstrated that an N-terminal conserved region of human Atg3 (hAtg3) communicates informati...
BiophysicsEnzymesSolution-state NMR
10.1038/S41467-020-20607-0
ISSN:2041-1723
Target-aware 3D molecular generation based on guided equivariant diffusion
Qiaoyu Hu•Changzhi Sun•Huan He•Jiazheng Xu•Danlin Liu等 9 人
Nature Communications
2025
•2025/8/25
•Vol.16 No.1 p.1-17
Recent molecular generation models for structure-based drug design (SBDD) often produce unrealistic 3D molecules due to the neglect of structural feasibility and drug-like properties. In this paper, we introduce DiffGui, a target-conditioned E(3)-equivariant diffusion model that integrates bond diff...
Computational chemistryComputational modelsMachine learning
10.1038/S41467-025-63245-0
ISSN:2041-1723
Stepwise transcription stalling by the anti-cancer drug Actinomycin D and insights into short tandem repeat transcription inhibition
Weiqi Zhao•Liulian Zhu•Yankai Liu•Wenjing Deng•Xu Yang等 11 人
Nature Communications
2026
•2026/3/15
0Short tandem repeats (STRs) comprise 6% of the human genome, and their transcription is linked to over 60 diseases. Actinomycin D (ACTD) is the first clinically approved anticancer antibiotic that inhibits transcription through an incompletely understood mechanism. Here, using reconstituted yeast an...
Cryoelectron microscopyTranscription
10.1038/S41467-026-70612-Y
ISSN:2041-1723
O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology
Aaron T. Balana•Anne-Laure Mahul-Mellier•Binh A. Nguyen•Mian Horvath•Afraah Javed等 16 人
Nature Chemical Biology
2024
•2024/2/12
•00 p.1-10
Amyloid-forming proteins such α-synuclein and tau, which are implicated in Alzheimer’s and Parkinson’s disease, can form different fibril structures or strains with distinct toxic properties, seeding activities and pathology. Understanding the determinants contributing to the formation of different ...
GlycobiologyPost-translational modificationsProtein aggregationProteins
10.1038/S41589-024-01551-2
ISSN:1552-4450
Deep-learning structure elucidation from single-mutant deep mutational scanning
Zachary C. Drake•Elijah H. Day•Paul D. Toth•Steffen Lindert
Nature Communications
2025
•2025/7/25
•Vol.16 No.1 p.1-12
Deep learning has revolutionized the field of protein structure prediction. AlphaFold2, a deep neural network, vastly outperformed previous algorithms to provide near atomic-level accuracy when predicting protein structures. Despite its success, there still are limitations which prevent accurate pre...
Data integrationMachine learningProtein structure predictions
10.1038/S41467-025-62261-4
ISSN:2041-1723
Crystal structure of adenosine A2A receptor in complex with clinical candidate Etrumadenant reveals unprecedented antagonist interaction
Tobias Claff•Jonathan G. Schlegel•Jan H. Voss•Victoria J. Vaaßen•Renato H. Weiße等 10 人
Communications Chemistry
2023
•2023/6/1
•Vol.6 No.1 p.1-10
The Gs protein-coupled adenosine A2A receptor (A2AAR) represents an emerging drug target for cancer immunotherapy. The clinical candidate Etrumadenant was developed as an A2AAR antagonist with ancillary blockade of the A2BAR subtype. It constitutes a unique chemotype featuring a poly-substitute...
G protein-coupled receptorsMechanism of actionMedicinal chemistryX-ray crystallography
10.1038/S42004-023-00894-6
ISSN:2399-3669
Development of an ultrahigh affinity, trimeric ACE2 biologic as a universal SARS-CoV-2 antagonist
Juliet Gonzales•Tynan Young•Hyeran Choi•Miso Park•Yead Jewel等 9 人
Communications Biology
2025
•2025/10/6
•Vol.8 No.1 p.1-15
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, utilizes membrane-bound, angiotensin-converting enzyme II (ACE2) for internalization and infection. We describe the development of a biologic that takes advantage of the proximity of the N-terminus o...
BiophysicsCryoelectron microscopyMolecular biophysicsThermodynamicsX-ray crystallography
10.1038/S42003-025-08819-W
ISSN:2399-3642
Routine sub-2.5 Å cryo-EM structure determination of GPCRs
Radostin Danev•Matthew Belousoff•Yi-Lynn Liang•Xin Zhang•Fabian Eisenstein等 7 人
Nature Communications
2021
•2021/7/15
•Vol.12 No.1 p.1-10
Cryo-electron microscopy (cryo-EM) of small membrane proteins, such as G protein-coupled receptors (GPCRs), remains challenging. Pushing the performance boundaries of the technique requires quantitative knowledge about the contribution of multiple factors. Here, we present an in-depth analysis and o...
Cryoelectron microscopyReceptor pharmacologyStructural biology
10.1038/S41467-021-24650-3
ISSN:2041-1723
TAPBPR employs a ligand-independent docking mechanism to chaperone MR1 molecules
McShan Andrew C.•Devlin Christine A.•Papadaki Georgia F.•Sun Yi•Green Adam I.等 9 人
Nature Chemical Biology
2022
•2022/6/20
•00 p.1-10
Chaperones tapasin and transporter associated with antigen processing (TAP)-binding protein related (TAPBPR) associate with the major histocompatibility complex (MHC)-related protein 1 (MR1) to promote trafficking and cell surface expression. However, the binding mechanism and ligand dependency of M...
Mechanism of actionNMR spectroscopy
10.1038/S41589-022-01049-9
ISSN:1552-4450
Structural insights into how Prp5 proofreads the pre-mRNA branch site
Zhang Zhenwei•Rigo Norbert•Dybkov Olexandr•Fourmann Jean-Baptiste•Will Cindy L.等 9 人
Nature
2021
•2021/8/4
•Vol.596 No.7871 p.296-300
During the splicing of introns from precursor messenger RNAs (pre-mRNAs), the U2 small nuclear ribonucleoprotein (snRNP) must undergo stable integration into the spliceosomal A complex—a poorly understood, multistep process that is facilitated by the DEAD-box helicase Prp5 (refs. 1–4). During this p...
Cryoelectron microscopyRNA splicing
10.1038/S41586-021-03789-5
ISSN:0028-0836
Substrate selectivity of the human RNA m5C methyltransferase NSUN2
Jacob Canepa•Victor M. Ruiz-Arroyo•Netanya S. Schlamowitz•Yunsun Nam
Nature
2026
•2026/5/27
•00 p.1-8
Specific deposition of RNA modifications is important for regulating gene expression1,2. 5-Methylcytosine (m5C) is a common epitranscriptomic modification, and NSUN2 is a key enzyme responsible for m5C methylation of various types of RNA. Dysregulation of NSUN2 is associated with numerous diseases, ...
Cryoelectron microscopyEnzyme mechanismsRNA
10.1038/S41586-026-10582-9
ISSN:0028-0836
A pleurocidin analogue with greater conformational flexibility, enhanced antimicrobial potency and in vivo therapeutic efficacy
Giorgia Manzo•Charlotte K. Hind•Philip M. Ferguson•Richard T. Amison•Alice C. Hodgson-Casson等 22 人
Communications Biology
2020
•2020/11/27
•Vol.3 No.1 p.1-16
Antimicrobial peptides (AMPs) are a potential alternative to classical antibiotics that are yet to achieve a therapeutic breakthrough for treatment of systemic infections. The antibacterial potency of pleurocidin, an AMP from Winter Flounder, is linked to its ability to cross bacterial plasma membra...
AntibioticsComputational biophysicsMembrane biophysicsMetabolomics
10.1038/S42003-020-01420-3
ISSN:2399-3642
Improving the generalizability of protein-ligand binding predictions with AI-Bind
Chatterjee Ayan•Walters Robin•Shafi Zohair•Ahmed Omair Shafi•Sebek Michael等 10 人
Nature Communications
2023
•2023/4/8
•Vol.14 No.1 p.1-15
Identifying novel drug-target interactions is a critical and rate-limiting step in drug discovery. While deep learning models have been proposed to accelerate the identification process, here we show that state-of-the-art models fail to generalize to novel (i.e., never-before-seen) structures. We un...
Complex networksHigh-throughput screeningMachine learningMolecular modelling
10.1038/S41467-023-37572-Z
ISSN:2041-1723
Genomics 2 Proteins portal: a resource and discovery tool for linking genetic screening outputs to protein sequences and structures
Seulki Kwon•Jordan Safer•Duyen T. Nguyen•David Hoksza•Patrick May等 10 人
Nature Methods
2024
•2024/9/18
•Vol.21 No.10 p.1947-1957
Recent advances in AI-based methods have revolutionized the field of structural biology. Concomitantly, high-throughput sequencing and functional genomics have generated genetic variants at an unprecedented scale. However, efficient tools and resources are needed to link disparate data types—to ‘map...
Computational platforms and environmentsData integrationDatabasesProteome informatics
10.1038/S41592-024-02409-0
ISSN:1548-7091
Density-driven support fields for topological stability in protein structures
Jianshi Wang•Yukio Ohsawa
Npj Biological Physics And Mechanics
2026
•2026/7/6
•Vol.3 No.1 p.100
We model protein structural stability as a continuous scalar quantity defined over molecular geometry, referred to as the support field. Instead of treating stability as a discrete residue annotation or an empirical score, this representation characterizes protein folds through the combined effects ...
Computational biology and bioinformaticsDrug discoveryMathematics and computing
10.1038/S44341-026-00040-Y
ISSN:3004-863X
PEN1 catalyses RNA primer removal during plastid DNA replication in maize
Xing Huang•Guolong Shi•Qiao Xiao•Jiaojiao Feng•Yongcai Huang等 15 人
Nature Plants
2025
•2025/6/25
•Vol.11 No.7 p.1325-1338
The plastid DNA (ptDNA) replication is initiated by primases, which synthesize RNA primers; following the synthesis of DNA fragments, primers must be removed before ligation. However, the enzymes and mechanisms underlying this process are poorly understood. Here we cloned a gene from maize that enco...
ChloroplastsPlant molecular biology
10.1038/S41477-025-02027-4
ISSN:2055-0278
NMR investigation of FOXO4-DNA interaction for discriminating target and non-target DNA sequences
Donghoon Kang•Min June Yang•Hae-Kap Cheong•Chin-Ju Park
Communications Biology
2024
•2024/11/1
•Vol.7 No.1 p.1-10
Forkhead box O4 (FOXO4), a human transcription factor, recognizes target DNA through its forkhead domain (FHD) while maintaining comparable binding affinity to non-target DNA. The conserved region 3 (CR3), a transactivation domain, modulates DNA binding kinetics to FHD and contributes to target DNA ...
DNA-binding proteinsSolution-state NMR
10.1038/S42003-024-07133-1
ISSN:2399-3642
Molecular insights into species-specific ACE2 recognition of coronavirus HKU5
Yuanyuan Zhang•Yuya Li•Weijie Gao•Dexin Li•Lingyun Xia等 6 人
Nature Communications
2025
•2025/12/4
•Vol.16 No.1 p.108890
Coronaviruses represent a significant zoonotic threat, with host adaptation serving as a pivotal determinant of cross-species transmission. The bat-derived β-coronavirus HKU5 utilizes its spike (S) protein for receptor recognition and viral entry. Here, we report the cryo-electron microscopy (cryo-E...
Cryoelectron microscopyVirus–host interactions
10.1038/S41467-025-65883-W
ISSN:2041-1723
Molecular determinants for the association of human hormone-sensitive lipase with lipid droplets
Han Peng•Qikui Xu•Ting Zhang•Jiakai Zhu•Jinheng Pan等 9 人
Nature Communications
2025
•2025/4/12
•Vol.16 No.1 p.1-19
Lipid droplets (LDs) are the main cellular storage sites for triacylglycerols (TAGs), playing an important role in energy homeostasis and cell signaling. Hydrolysis of the stored TAGs begins with conversion of TAGs into diacylglycerols (DAGs) by adipose triglyceride lipase (ATGL), followed by hydrol...
Cryoelectron microscopyHydrolasesLipidsMolecular biophysicsStructural biology
10.1038/S41467-025-58887-Z
ISSN:2041-1723
Three distinct strategies lead to programmable aliphatic C−H oxidation in bicyclomycin biosynthesis
Lian Wu•Jun-Bin He•Wanqing Wei•Hai-Xue Pan•Xin Wang等 9 人
Nature Communications
2025
•2025/5/19
•Vol.16 No.1 p.1-13
The C−H bond functionalization has been widely used in chemical synthesis over the past decade. However, regio- and stereoselectivity still remain a significant challenge, especially for inert aliphatic C−H bonds. Here we report the mechanism of three Fe(II)/α-ketoglutarate-dependent dioxygenases in...
BiocatalysisEnzymesOxidoreductasesX-ray crystallography
10.1038/S41467-025-58997-8
ISSN:2041-1723
LABind: identifying protein binding ligand-aware sites via learning interactions between ligand and protein
Zhijun Zhang•Lijun Quan•Junkai Wang•Liangchen Peng•Qiufeng Chen等 12 人
Nature Communications
2025
•2025/8/19
•Vol.16 No.1 p.1-14
Protein-ligand interactions are crucial for understanding various biological processes and drug discovery and design. However, experimental methods are costly; single-ligand-oriented methods are tailored to specific ligands; multi-ligand-oriented methods are constrained by the lack of ligand encodin...
Computational biology and bioinformaticsComputational modelsProtein function predictions
10.1038/S41467-025-62899-0
ISSN:2041-1723
trRosettaRNA: automated prediction of RNA 3D structure with transformer network
Wenkai Wang•Chenjie Feng•Renmin Han•Ziyi Wang•Lisha Ye等 10 人
Nature Communications
2023
•2023/11/9
•Vol.14 No.1 p.1-13
RNA 3D structure prediction is a long-standing challenge. Inspired by the recent breakthrough in protein structure prediction, we developed trRosettaRNA, an automated deep learning-based approach to RNA 3D structure prediction. The trRosettaRNA pipeline comprises two major steps: 1D and 2D geometrie...
Computational modelsMachine learningMolecular modellingSoftware
10.1038/S41467-023-42528-4
ISSN:2041-1723
A specific inhibitor of ALDH1A3 regulates retinoic acid biosynthesis in glioma stem cells
Li Jianfeng•Garavaglia Silvia•Ye Zhaofeng•Moretti Andrea•Belyaeva Olga V.等 20 人
Communications Biology
2021
•2021/12/21
•Vol.4 No.1 p.1-16
Elevated aldehyde dehydrogenase (ALDH) activity correlates with poor outcome for many solid tumors as ALDHs may regulate cell proliferation and chemoresistance of cancer stem cells (CSCs). Accordingly, potent, and selective inhibitors of key ALDH enzymes may represent a novel CSC-directed treatment ...
CancerDrug discoveryStructural biology
10.1038/S42003-021-02949-7
ISSN:2399-3642
Structure of the yeast ceramide synthase
Jan-Hannes Schäfer•Lena Clausmeyer•Carolin Körner•Bianca M. Esch•Verena N. Wolf等 12 人
Nature Structural & Molecular Biology
2024
•2024/11/11
•00 p.1-9
Ceramides are essential lipids involved in forming complex sphingolipids and acting as signaling molecules. They result from the N-acylation of a sphingoid base and a CoA-activated fatty acid, a reaction catalyzed by the ceramide synthase (CerS) family of enzymes. Yet, the precise structural details...
Cryoelectron microscopyMembrane lipidsMembrane proteins
10.1038/S41594-024-01415-2
ISSN:1545-9993
Structural basis of phosphate export by human XPR1
Yifei Wang•Yuechan Wang•Hui Yang•Ao Li•Dan Ma等 6 人
Cell Research
2025
•2025/2/28
•00 p.1-4
Cancer metabolismElectron microscopy
10.1038/S41422-025-01081-Z
ISSN:1748-7838
Parahydrogen-enhanced magnetic resonance identification of intermediates in [Fe]-hydrogenase catalysis
Lukas Kaltschnee•Andrey N. Pravdivtsev•Manuel Gehl•Gangfeng Huang•Georgi L. Stoychev等 13 人
Nature Catalysis
2024
•2024/12/13
•Vol.7 No.12 p.1417-1429
Hydrogenases are widespread metalloenzymes used for the activation and production of molecular hydrogen. Understanding the catalytic mechanism of hydrogenases can help to establish industrial (bio)catalytic hydrogen production and conversion. Here we show the observation of so-far undetectable inter...
BiocatalysisEnzyme mechanismsNMR spectroscopyOxidoreductases
10.1038/S41929-024-01262-W
ISSN:2520-1158
Comprehensive characterization of protein–protein interactions perturbed by disease mutations
Feixiong Cheng•Junfei Zhao•Yang Wang•Weiqiang Lu•Zehui Liu等 24 人
Nature Genetics
2021
•2021/2/8
•Vol.53 No.3 p.342-353
Technological and computational advances in genomics and interactomics have made it possible to identify how disease mutations perturb protein–protein interaction (PPI) networks within human cells. Here, we show that disease-associated germline variants are significantly enriched in sequences encodi...
Computational biology and bioinformaticsGeneticsStructural biologySystems biology
10.1038/S41588-020-00774-Y
ISSN:1061-4036
Crystal structures of monomeric BsmI restriction endonuclease reveal coordinated sequential cleavage of two DNA strands
Rémi Sieskind•Sophia Missoury•Clément Madru•Isciane Commenge•Germain Niogret等 11 人
Communications Biology
2025
•2025/3/7
•Vol.8 No.1 p.1-13
BsmI, a thermophilic Type IIS restriction endonuclease from Bacillus stearothermophilus, presents a unique structural composition, housing two distinct active sites within a single monomer. Recognition of the non-symmetrical 5’-GAATGC-3’ sequence enables precise cleavage of the top and bottom DNA st...
Enzyme mechanismsX-ray crystallography
10.1038/S42003-025-07612-Z
ISSN:2399-3642
Isoform- and ligand-specific modulation of the adhesion GPCR ADGRL3/Latrophilin3 by a synthetic binder
Kordon Szymon P.•Dutka Przemysław•Adamska Justyna M.•Bandekar Sumit J.•Leon Katherine等 10 人
Nature Communications
2023
•2023/2/6
•Vol.14 No.1 p.1-13
Adhesion G protein-coupled receptors (aGPCRs) are cell-surface proteins with large extracellular regions that bind to multiple ligands to regulate key biological functions including neurodevelopment and organogenesis. Modulating a single function of a specific aGPCR isoform while affecting no other ...
Cell signallingG protein-coupled receptorsX-ray crystallography
10.1038/S41467-023-36312-7
ISSN:2041-1723
“Redirecting an anti-IL-1β antibody to bind a new, unrelated and computationally predicted epitope on hIL-17A”
Sharon Fischman•Itay Levin•Jean-Michel Rondeau•Marek Štrajbl•Sylvie Lehmann等 23 人
Communications Biology
2023
•2023/9/29
•Vol.6 No.1 p.1-13
Antibody engineering technology is at the forefront of therapeutic antibody development. The primary goal for engineering a therapeutic antibody is the generation of an antibody with a desired specificity, affinity, function, and developability profile. Mature antibodies are considered antigen speci...
BiologicsProtein designX-ray crystallography
10.1038/S42003-023-05369-X
ISSN:2399-3642
Structural effects of the highly protective V127 polymorphism on human prion protein
Laszlo L. P. Hosszu•Rebecca Conners•Daljit Sangar•Mark Batchelor•Elizabeth B. Sawyer等 14 人
Communications Biology
2020
•2020/7/29
•Vol.3 No.1 p.1-12
Prion diseases, a group of incurable, lethal neurodegenerative disorders of mammals including humans, are caused by prions, assemblies of misfolded host prion protein (PrP). A single point mutation (G127V) in human PrP prevents prion disease, however the structural basis for its protective effect re...
Prion diseasesSolution-state NMR
10.1038/S42003-020-01126-6
ISSN:2399-3642
A refined picture of the native amine dehydrogenase family revealed by extensive biodiversity screening
Eddy Elisée•Laurine Ducrot•Raphaël Méheust•Karine Bastard•Aurélie Fossey-Jouenne等 13 人
Nature Communications
2024
•2024/6/10
•Vol.15 No.1 p.1-15
Native amine dehydrogenases offer sustainable access to chiral amines, so the search for scaffolds capable of converting more diverse carbonyl compounds is required to reach the full potential of this alternative to conventional synthetic reductive aminations. Here we report a multidisciplinary stra...
BiocatalysisData miningFunctional clusteringOxidoreductases
10.1038/S41467-024-49009-2
ISSN:2041-1723
Design of functionalised circular tandem repeat proteins with longer repeat topologies and enhanced subunit contact surfaces
Hallinan Jazmine P.•Doyle Lindsey A.•Shen Betty W.•Gewe Mesfin M.•Takushi Brittany等 10 人
Communications Biology
2021
•2021/10/29
•Vol.4 No.1 p.1-14
Circular tandem repeat proteins (‘cTRPs’) are de novo designed protein scaffolds (in this and prior studies, based on antiparallel two-helix bundles) that contain repeated protein sequences and structural motifs and form closed circular structures. They can display significant stability and solubili...
NanobiotechnologyProteinsX-ray crystallography
10.1038/S42003-021-02766-Y
ISSN:2399-3642
Origins of glycan selectivity in streptococcal Siglec-like adhesins suggest mechanisms of receptor adaptation
Bensing Barbara A.•Stubbs Haley E.•Agarwal Rupesh•Yamakawa Izumi•Luong Kelvin等 18 人
Nature Communications
2022
•2022/5/18
•Vol.13 No.1 p.1-14
Bacterial binding to host receptors underlies both commensalism and pathogenesis. Many streptococci adhere to protein-attached carbohydrates expressed on cell surfaces using Siglec-like binding regions (SLBRs). The precise glycan repertoire recognized may dictate whether the organism is a strict com...
GlycobiologyLectinsPathogensX-ray crystallography
10.1038/S41467-022-30509-Y
ISSN:2041-1723
Structural basis for activation of DNMT1
Kikuchi Amika•Onoda Hiroki•Yamaguchi Kosuke•Kori Satomi•Matsuzawa Shun等 18 人
Nature Communications
2022
•2022/11/21
•Vol.13 No.1 p.1-11
DNMT1 is an essential enzyme that maintains genomic DNA methylation, and its function is regulated by mechanisms that are not yet fully understood. Here, we report the cryo-EM structure of human DNMT1 bound to its two natural activators: hemimethylated DNA and ubiquitinated histone H3. We find that ...
Cryoelectron microscopyDNA methylation
10.1038/S41467-022-34779-4
ISSN:2041-1723
High-affinity peptides developed against calprotectin and their application as synthetic ligands in diagnostic assays
Cristina Díaz-Perlas•Benjamin Ricken•Lluc Farrera-Soler•Dmitrii Guschin•Florence Pojer等 8 人
Nature Communications
2023
•2023/5/17
•Vol.14 No.1 p.1-14
Common inflammatory disorders such as ulcerative colitis and Crohn’s disease are non-invasively diagnosed or monitored by the biomarker calprotectin. However, current quantitative tests for calprotectin are antibody-based and vary depending on the type of antibody and assay used. Additionally, the b...
Biomedical engineeringCombinatorial librariesDiagnostic markersDiagnosticsPeptides
10.1038/S41467-023-38075-7
ISSN:2041-1723
Structural insight into the substrate recognition and transport mechanism of amino acid transporter complex ACE2-B0AT1 and ACE2-SIT1
Yaning Li•Yiming Chen•Yuanyuan Zhang•Yaping Shen•Kangtai Xu等 8 人
Cell Discovery
2023
•2023/9/8
•Vol.9 No.1 p.1-5
Cryoelectron microscopyMechanisms of disease
10.1038/S41421-023-00596-2
ISSN:2056-5968
Drug inhibition and substrate transport mechanisms of human VMAT2
Feiwen Wei•Huihui Liu•Wei Zhang•Jufang Wang•Yanqing Zhang
Nature Communications
2025
•2025/1/2
•Vol.16 No.1 p.1-11
Vesicular monoamine transporter 2 (VMAT2) is crucial for packaging monoamine neurotransmitters into synaptic vesicles, with their dysregulation linked to schizophrenia, mood disorders, and Parkinson’s disease. Tetrabenazine (TBZ) and valbenazine (VBZ), both FDA-approved VMAT2 inhibitors, are employe...
Cryoelectron microscopyTransporters in the nervous system
10.1038/S41467-024-55361-0
ISSN:2041-1723
SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability
Antonella Lettieri•Roberto Oleari•Marleen Hester van den Munkhof•Eljo Yvette van Battum•Marieke Geerte Verhagen等 18 人
Nature Communications
2023
•2023/12/7
•Vol.14 No.1 p.1-20
Innervation of the hypothalamic median eminence by Gonadotropin-Releasing Hormone (GnRH) neurons is vital to ensure puberty onset and successful reproduction. However, the molecular and cellular mechanisms underlying median eminence development and pubertal timing are incompletely understood. Here w...
Disease modelEndocrine reproductive disordersNeuro–vascular interactions
10.1038/S41467-023-43820-Z
ISSN:2041-1723
The small molecule inhibitor of SARS-CoV-2 3CLpro EDP-235 prevents viral replication and transmission in vivo
Michael H. J. Rhodin•Archie C. Reyes•Anand Balakrishnan•Nalini Bisht•Nicole M. Kelly等 28 人
Nature Communications
2024
•2024/8/1
•Vol.15 No.1 p.1-12
The COVID-19 pandemic has led to the deaths of millions of people and severe global economic impacts. Small molecule therapeutics have played an important role in the fight against SARS-CoV-2, the virus responsible for COVID-19, but their efficacy has been limited in scope and availability, with man...
Molecular medicinePharmaceuticsSARS-CoV-2SARS virusViral infection
10.1038/S41467-024-50931-8
ISSN:2041-1723
Distinct evolution of type I glutamine synthetase in Plasmodium and its species-specific requirement
Sourav Ghosh•Rajib Kundu•Manjunatha Chandana•Rahul Das•Aditya Anand等 17 人
Nature Communications
2023
•2023/7/14
•Vol.14 No.1 p.1-27
Malaria parasite lacks canonical pathways for amino acid biosynthesis and depends primarily on hemoglobin degradation and extracellular resources for amino acids. Interestingly, a putative gene for glutamine synthetase (GS) is retained despite glutamine being an abundant amino acid in human and mosq...
EnzymesParasite biology
10.1038/S41467-023-39670-4
ISSN:2041-1723
General transcription factor from Escherichia coli with a distinct mechanism of action
Nikita Vasilyev•Mengjie M. J. Liu•Vitaly Epshtein•Ilya Shamovsky•Evgeny Nudler
Nature Structural & Molecular Biology
2024
•2024/1/4
•00 p.1-9
Gene expression in Escherichia coli is controlled by well-established mechanisms that activate or repress transcription. Here, we identify CedA as an unconventional transcription factor specifically associated with the RNA polymerase (RNAP) σ70 holoenzyme. Structural and biochemical analysis of CedA...
Cellular microbiologyCryoelectron microscopyMass spectrometryTranscriptional regulatory elements
10.1038/S41594-023-01154-W
ISSN:1545-9993
Activation mechanism of a small prototypic Rec-GGDEF diguanylate cyclase
Raphael D. Teixeira•Fabian Holzschuh•Tilman Schirmer
Nature Communications
2021
•2021/4/12
•Vol.12 No.1 p.1-15
Diguanylate cyclases synthesising the bacterial second messenger c-di-GMP are found to be regulated by a variety of sensory input domains that control the activity of their catalytical GGDEF domain, but how activation proceeds mechanistically is, apart from a few examples, still largely unknown. As ...
Bacterial structural biologyEnzyme mechanismsMolecular modellingX-ray crystallography
10.1038/S41467-021-22492-7
ISSN:2041-1723
Plant carbonic anhydrase-like enzymes in neuroactive alkaloid biosynthesis
Ryan S. Nett•Yaereen Dho•Chun Tsai•Daria Passow•Jaime Martinez Grundman等 7 人
Nature
2023
•2023/11/8
•00 p.1-10
Plants synthesize numerous alkaloids that mimic animal neurotransmitters1. The diversity of alkaloid structures is achieved through the generation and tailoring of unique carbon scaffolds2,3, yet many neuroactive alkaloids belong to a scaffold class for which no biosynthetic route or enzyme catalyst...
BiosynthesisEnzymesNatural productsSecondary metabolism
10.1038/S41586-023-06716-Y
ISSN:0028-0836
Low- N protein engineering with data-efficient deep learning
Surojit Biswas•Grigory Khimulya•Ethan C. Alley•Kevin M. Esvelt•George M. Church
Nature Methods
2021
•2021/4/7
•Vol.18 No.4 p.389-396
Protein engineering has enormous academic and industrial potential. However, it is limited by the lack of experimental assays that are consistent with the design goal and sufficiently high throughput to find rare, enhanced variants. Here we introduce a machine learning-guided paradigm that can use a...
Machine learningProtein design
10.1038/S41592-021-01100-Y
ISSN:1548-7091
A broad-spectrum virus- and host-targeting peptide against respiratory viruses including influenza virus and SARS-CoV-2
Hanjun Zhao•Kelvin K. W. To•Kong-Hung Sze•Timothy Tin-Mong Yung•Mingjie Bian等 10 人
Nature Communications
2020
•2020/8/25
•Vol.11 No.1 p.1-10
The 2019 novel respiratory virus (SARS-CoV-2) causes COVID-19 with rapid global socioeconomic disruptions and disease burden to healthcare. The COVID-19 and previous emerging virus outbreaks highlight the urgent need for broad-spectrum antivirals. Here, we show that a defensin-like peptide P9R exhib...
AntiviralsDrug discoveryInfluenza virusSARS-CoV-2
10.1038/S41467-020-17986-9
ISSN:2041-1723
Mechanism of molybdate insertion into pterin-based molybdenum cofactors
Corinna Probst•Jing Yang•Joern Krausze•Thomas W. Hercher•Casseday P. Richers等 12 人
Nature Chemistry
2021
•2021/6/28
•00 p.1-8
The molybdenum cofactor (Moco) is found in the active site of numerous important enzymes that are critical to biological processes. The bidentate ligand that chelates molybdenum in Moco is the pyranopterin dithiolene (molybdopterin, MPT). However, neither the mechanism of molybdate insertion into MP...
BiocatalysisBiosynthesisMetalloproteins
10.1038/S41557-021-00714-1
ISSN:1755-4330
Fibroblastic reticular cells direct the initiation of T cell responses via CD44
Xavier Y. X. Sng•Valentina Voigt•Iona S. Schuster•Peter Fleming•Felix A. Deuss等 23 人
Nature
2026
•2026/1/21
•Vol.651 No.8106 p.752-762
The movement of dendritic cells and T cells within secondary lymphoid organs is critical for the development of adaptive immune responses1,2. Central to this process is the fibroblastic reticular cell (FRC) network, which forms a highly organized conduit system that facilitates the movement of and i...
Cell migrationImmune evasionLymphocyte activationSpleenVirus–host interactions
10.1038/S41586-025-09988-8
ISSN:0028-0836
Sensitive identification of neoantigens and cognate TCRs in human solid tumors
Arnaud Marion•Chiffelle Johanna•Genolet Raphael•Navarro Rodrigo Blanca•Perez Marta A. S.等 22 人
Nature Biotechnology
2021
•2021/11/15
•00 p.1-5
The identification of patient-specific tumor antigens is complicated by the low frequency of T cells specific for each tumor antigen. Here we describe NeoScreen, a method that enables the sensitive identification of rare tumor (neo)antigens and of cognate T cell receptors (TCRs) expressed by tumor-i...
Cancer immunotherapyT-cell receptorTranslational research
10.1038/S41587-021-01072-6
ISSN:1087-0156
ELOF1 is a transcription-coupled DNA repair factor that directs RNA polymerase II ubiquitylation
Yana van der Weegen•Klaas de Lint•Diana van den Heuvel•Yuka Nakazawa•Tycho E. T. Mevissen等 23 人
Nature Cell Biology
2021
•2021/6/9
•Vol.23 No.6 p.595-607
Cells employ transcription-coupled repair (TCR) to eliminate transcription-blocking DNA lesions. DNA damage-induced binding of the TCR-specific repair factor CSB to RNA polymerase II (RNAPII) triggers RNAPII ubiquitylation of a single lysine (K1268) by the CRL4CSA ubiquitin ligase. How CRL4CSA is sp...
DNA damage and repairDNA replicationTranscriptionUbiquitylation
10.1038/S41556-021-00688-9
ISSN:1465-7392
Hedgehog-Interacting Protein is a multimodal antagonist of Hedgehog signalling
Griffiths Samuel C.•Schwab Rebekka A.•El Omari Kamel•Bishop Benjamin•Iverson Ellen J.等 12 人
Nature Communications
2021
•2021/12/9
•Vol.12 No.1 p.1-13
Hedgehog (HH) morphogen signalling, crucial for cell growth and tissue patterning in animals, is initiated by the binding of dually lipidated HH ligands to cell surface receptors. Hedgehog-Interacting Protein (HHIP), the only reported secreted inhibitor of Sonic Hedgehog (SHH) signalling, binds dire...
Extracellular signalling moleculesMembrane proteinsMorphogen signallingSterolsX-ray crystallography
10.1038/S41467-021-27475-2
ISSN:2041-1723
UBE2A and UBE2B are recruited by an atypical E3 ligase module in UBR4
Lucy Barnsby-Greer•Peter D. Mabbitt•Marc-Andre Dery•Daniel R. Squair•Nicola T. Wood等 8 人
Nature Structural & Molecular Biology
2024
•2024/1/5
•00 p.1-13
UBR4 is a 574 kDa E3 ligase (E3) of the N-degron pathway with roles in neurodevelopment, age-associated muscular atrophy and cancer. The catalytic module that carries out ubiquitin (Ub) transfer remains unknown. Here we identify and characterize a distinct E3 module within human UBR4 consisting of a...
LigasesUbiquitin ligasesUbiquitylationX-ray crystallography
10.1038/S41594-023-01192-4
ISSN:1545-9993
Structural insight into the assembly and working mechanism of helicase-primase D5 from Mpox virus
Yaning Li•Jing Zhu•Yingying Guo•Renhong Yan
Nature Structural & Molecular Biology
2024
•2024/1/4
•00 p.1-14
The Mpox pandemic, caused by the Mpox virus (or monkeypox virus, MPXV), has gained global attention. The D5 protein, a putative helicase-primase found in MPXV, plays a vital role in viral replication and genome uncoating. Here we determined multiple cryo-EM structures of full-length hexameric D5 in ...
DNA replicationElectron microscopy
10.1038/S41594-023-01142-0
ISSN:1545-9993
Structural basis for different ω-agatoxin IVA sensitivities of the P-type and Q-type Cav2.1 channels
Zhangqiang Li•Ye Cong•Tong Wu•Tongtong Wang•Xinyao Lou等 7 人
Cell Research
2024
•2024/3/5
•00 p.1-3
Cryoelectron microscopyMolecular modelling
10.1038/S41422-024-00940-5
ISSN:1748-7838
An E1–E2 fusion protein primes antiviral immune signalling in bacteria
Ledvina Hannah E.•Ye Qiaozhen•Gu Yajie•Sullivan Ashley E.•Quan Yun等 9 人
Nature
2023
•2023/2/8
•00 p.1-7
In all organisms, innate immune pathways sense infection and rapidly activate potent immune responses while avoiding inappropriate activation (autoimmunity). In humans, the innate immune receptor cyclic GMP–AMP synthase (cGAS) detects viral infection to produce the nucleotide second messenger cyclic...
Bacterial structural biologyBacteriophagesCryoelectron microscopyInnate immunity
10.1038/S41586-022-05647-4
ISSN:0028-0836
Structures of Helicobacter pylori C-terminal protease CtpA reveal a new mode of self-contained proteolytic processing
Kailei Sun•Lili Yan•Chin Yu Mok•Pui Kin So•Sirius Pui Kam Tse等 9 人
Communications Biology
2025
•2025/11/22
0Bacterial carboxyl-terminal processing proteases (CTPs) are essential for protein quality control, signal transduction, and cell adaptation. Typically, activation of CTPs involves substrate binding to the PDZ domain or an adaptor protein. Recent studies of CTPs from various bacterial species have in...
Cryoelectron microscopyHydrolases
10.1038/S42003-025-09175-5
ISSN:2399-3642
Unexpected enzyme-catalysed [4+2] cycloaddition and rearrangement in polyether antibiotic biosynthesis
Rory Little•Fernanda C. R. Paiva•Robert Jenkins•Hui Hong•Yuhui Sun等 11 人
Nature Catalysis
2019
•2019/10/14
•Vol.2 No.11 p.1045-1054
Enzymes that catalyse remarkable Diels–Alder-like [4+2] cyclizations have been previously implicated in the biosynthesis of spirotetronate and spirotetramate antibiotics. Biosynthesis of the polyether antibiotic tetronasin is not expected to require such steps, yet the tetronasin gene cluster encode...
Asymmetric catalysisBiocatalysisBiosynthesisEnzymesStructure elucidation
10.1038/S41929-019-0351-2
ISSN:2520-1158
Structure and mechanism of human diacylglycerol O -acyltransferase 1
Lie Wang•Hongwu Qian•Yin Nian•Yimo Han•Zhenning Ren等 11 人
Nature
2020
•2020/5/13
•Vol.581 No.7808 p.329-332
Diacylglycerol O-acyltransferase 1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans1. DGAT1 belongs to the membrane-bound O-acyltransferase (MBOAT) superfamily, members of which are found in all kingdoms of life and are involved in the acylat...
EnzymesStructural biology
10.1038/S41586-020-2280-2
ISSN:0028-0836
Assembly defects of human tRNA splicing endonuclease contribute to impaired pre-tRNA processing in pontocerebellar hypoplasia
Sekulovski Samoil•Devant Pascal•Panizza Silvia•Gogakos Tasos•Pitiriciu Anda等 14 人
Nature Communications
2021
•2021/9/28
•Vol.12 No.1 p.1-15
Introns of human transfer RNA precursors (pre-tRNAs) are excised by the tRNA splicing endonuclease TSEN in complex with the RNA kinase CLP1. Mutations in TSEN/CLP1 occur in patients with pontocerebellar hypoplasia (PCH), however, their role in the disease is unclear. Here, we show that intron excisi...
Mechanisms of diseaseRNARNA-binding proteinsX-ray crystallography
10.1038/S41467-021-25870-3
ISSN:2041-1723
Structure and mechanism of the methyltransferase ribozyme MTR1
Scheitl Carolin P. M.•Mieczkowski Mateusz•Schindelin Hermann•Höbartner Claudia
Nature Chemical Biology
2022
•2022/3/17
•00 p.1-9
RNA-catalyzed RNA methylation was recently shown to be part of the catalytic repertoire of ribozymes. The methyltransferase ribozyme MTR1 catalyzes the site-specific synthesis of 1-methyladenosine (m1A) in RNA, using O6-methylguanine (m6G) as a methyl group donor. Here, we report the crystal structu...
RNAX-ray crystallography
10.1038/S41589-022-00976-X
ISSN:1552-4450
Structural insight on assembly-line catalysis in terpene biosynthesis
Jacque L. Faylo•Trevor van Eeuwen•Hee Jong Kim•Jose J. Gorbea Colón•Benjamin A. Garcia等 7 人
Nature Communications
2021
•2021/6/9
•Vol.12 No.1 p.1-12
Fusicoccadiene synthase from Phomopsis amygdali (PaFS) is a unique bifunctional terpenoid synthase that catalyzes the first two steps in the biosynthesis of the diterpene glycoside Fusicoccin A, a mediator of 14-3-3 protein interactions. The prenyltransferase domain of PaFS generates geranylgeranyl ...
Cryoelectron microscopyEnzyme mechanismsMultienzyme complexes
10.1038/S41467-021-23589-9
ISSN:2041-1723
Distance-AF improves predicted protein structure models by AlphaFold2 with user-specified distance constraints
Yuanyuan Zhang•Zicong Zhang•Yuki Kagaya•Genki Terashi•Bowen Zhao等 7 人
Communications Biology
2025
•2025/9/30
•Vol.8 No.1 p.1-14
The three-dimensional structure provides essential information for understanding biological functions of proteins. To aid structure determination, computational prediction has been extensively studied. Despite significant progress, challenges remain on difficult targets, such as those with multiple ...
Protein structure predictionsStructural biology
10.1038/S42003-025-08783-5
ISSN:2399-3642
Discovery of bioactive microbial gene products in inflammatory bowel disease
Zhang Yancong•Bhosle Amrisha•Bae Sena•McIver Lauren J.•Pishchany Gleb等 21 人
Nature
2022
•2022/5/25
•00 p.1-7
Microbial communities and their associated bioactive compounds1–3 are often disrupted in conditions such as the inflammatory bowel diseases (IBD)4. However, even in well-characterized environments (for example, the human gastrointestinal tract), more than one-third of microbial proteins are unc...
Crohn's diseaseMetagenomicsMicrobiomeSequence annotationUlcerative colitis
10.1038/S41586-022-04648-7
ISSN:0028-0836
Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimmers as HIV-1 vaccine candidates
Zhang Yi-Nan•Paynter Jennifer•Antanasijevic Aleksandar•Allen Joel D.•Eldad Mor等 19 人
Nature Communications
2023
•2023/4/8
•Vol.14 No.1 p.1-29
Uncleaved prefusion-optimized (UFO) design can stabilize diverse HIV-1 envelope glycoproteins (Envs). Single-component, self-assembling protein nanoparticles (1c-SApNP) can display 8 or 20 native-like Env trimers as vaccine candidates. We characterize the biophysical, structural, and antigenic prope...
Germinal centresGlycobiologyProtein vaccinesRetrovirus
10.1038/S41467-023-37742-Z
ISSN:2041-1723
SE(3)-equivariant ternary complex prediction towards target protein degradation
Fanglei Xue•Meihan Zhang•Shuqi Li•Xinyu Gao•James A. Wohlschlegel等 8 人
Nature Communications
2025
•2025/7/1
•Vol.16 No.1 p.1-15
Targeted protein degradation (TPD) has rapidly emerged as a powerful modality for drugging previously “undruggable” proteins. TPD employs small molecules like PROTACs and molecular glue degraders (MGD) to induce target protein degradation via the formation of a ternary complex with an E3 ligase. How...
Computational modelsDrug screeningProtein databasesProtein structure predictions
10.1038/S41467-025-61272-5
ISSN:2041-1723
Structures of the archaerhodopsin-3 transporter reveal that disordering of internal water networks underpins receptor sensitization
Juan F. Bada Juarez•Peter J. Judge•Suliman Adam•Danny Axford•Javier Vinals等 15 人
Nature Communications
2021
•2021/1/27
•Vol.12 No.1 p.1-10
Many transmembrane receptors have a desensitized state, in which they are unable to respond to external stimuli. The family of microbial rhodopsin proteins includes one such group of receptors, whose inactive or dark-adapted (DA) state is established in the prolonged absence of light. Here, we prese...
Computational biophysicsMembrane biophysicsMembrane proteinsX-ray crystallography
10.1038/S41467-020-20596-0
ISSN:2041-1723
The discovery and structural basis of two distinct state-dependent inhibitors of BamA
Dawei Sun•Kelly M. Storek•Dimitry Tegunov•Ying Yang•Christopher P. Arthur等 31 人
Nature Communications
2024
•2024/10/8
•Vol.15 No.1 p.1-15
BamA is the central component of the essential β-barrel assembly machine (BAM), a conserved multi-subunit complex that dynamically inserts and folds β-barrel proteins into the outer membrane of Gram-negative bacteria. Despite recent advances in our mechanistic and structural understanding of BamA, t...
MicrobiologyStructural biology
10.1038/S41467-024-52512-1
ISSN:2041-1723
Diverse MarR bacterial regulators of auxin catabolism in the plant microbiome
Conway Jonathan M.•Walton William G.•Salas-González Isai•Law Theresa F.•Lindberg Chloe A.等 14 人
Nature Microbiology
2022
•2022/10/20
•Vol.7 No.11 p.1817-1833
Chemical signalling in the plant microbiome can have drastic effects on microbial community structure, and on host growth and development. Previously, we demonstrated that the auxin metabolic signal interference performed by the bacterial genus Variovorax via an auxin degradation locus was essential...
Microbial communitiesMicrobial ecologyPhylogenomicsSystems biologyX-ray crystallography
10.1038/S41564-022-01244-3
ISSN:2058-5276
Resistance mechanisms of SARS-CoV-2 3CLpro to the non-covalent inhibitor WU-04
Lijing Zhang•Xuping Xie•Hannan Luo•Runtong Qian•Yang Yang等 9 人
Cell Discovery
2024
•2024/4/9
•Vol.10 No.1 p.1-14
Drug resistance poses a significant challenge in the development of effective therapies against SARS-CoV-2. Here, we identified two double mutations, M49K/M165V and M49K/S301P, in the 3C-like protease (3CLpro) that confer resistance to a novel non-covalent inhibitor, WU-04, which is currently in pha...
Molecular biologyStructural biology
10.1038/S41421-024-00673-0
ISSN:2056-5968
Structure of human MUTYH and functional profiling of cancer-associated variants reveal an allosteric network between its [4Fe-4S] cluster cofactor and active site required for DNA repair
Carlos H. Trasviña-Arenas•Upeksha C. Dissanayake•Nikole Tamayo•Mohammad Hashemian•Wen-Jen Lin等 11 人
Nature Communications
2025
•2025/4/16
•Vol.16 No.1 p.1-16
MUTYH is a clinically important DNA glycosylase that thwarts mutations by initiating base-excision repair at 8-oxoguanine (OG):A lesions. The roles for its [4Fe-4S] cofactor in DNA repair remain enigmatic. Functional profiling of cancer-associated variants near the [4Fe-4S] cofactor reveals that mos...
Cancer geneticsDNAEnzyme mechanisms
10.1038/S41467-025-58361-W
ISSN:2041-1723
Architecture of the human NALCN channelosome
Zhou Lunni•Liu Haobin•Zhao Qingqing•Wu Jianping•Yan Zhen
Cell Discovery
2022
•2022/4/6
•Vol.8 No.1 p.1-11
NALCN regulates the resting membrane potential by mediating the Na+ leak current in neurons, and it functions as a channelosome in complex with FAM155A, UNC79, and UNC80. Dysfunction of the NALCN channelosome causes a broad range of neurological and developmental diseases called NALCN channelopathie...
Cryoelectron microscopyProtein–protein interaction networks
10.1038/S41421-022-00392-4
ISSN:2056-5968
Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV
Vercellino Irene•Sazanov Leonid A.
Nature
2021
•2021/10/6
•Vol.598 No.7880 p.364-367
The enzymes of the mitochondrial electron transport chain are key players of cell metabolism. Despite being active when isolated, in vivo they associate into supercomplexes1, whose precise role is debated. Supercomplexes CIII2CIV1-2 (refs. 2,3), CICIII2 (ref. 4) and CICIII2CIV (respirasome)5–10 exis...
BioenergeticsCryoelectron microscopyEnergy metabolismSupramolecular assembly
10.1038/S41586-021-03927-Z
ISSN:0028-0836
Structural basis for the inhibition mechanism of LAT1-4F2hc complex by JPH203
Ziwei Hu•Renhong Yan
Cell Discovery
2024
•2024/7/2
•Vol.10 No.1 p.1-3
Cryoelectron microscopyTumour biomarkers
10.1038/S41421-024-00697-6
ISSN:2056-5968
Prediction of inter-chain distance maps of protein complexes with 2D attention-based deep neural networks
Guo Zhiye•Liu Jian•Skolnick Jeffrey•Cheng Jianlin
Nature Communications
2022
•2022/11/15
•Vol.13 No.1 p.1-10
Residue-residue distance information is useful for predicting tertiary structures of protein monomers or quaternary structures of protein complexes. Many deep learning methods have been developed to predict intra-chain residue-residue distances of monomers accurately, but few methods can accurately ...
Machine learningProtein structure predictions
10.1038/S41467-022-34600-2
ISSN:2041-1723
PCprophet: a framework for protein complex prediction and differential analysis using proteomic data
Andrea Fossati•Chen Li•Federico Uliana•Fabian Wendt•Fabian Frommelt等 16 人
Nature Methods
2021
•2021/4/15
•Vol.18 No.5 p.520-527
Despite the availability of methods for analyzing protein complexes, systematic analysis of complexes under multiple conditions remains challenging. Approaches based on biochemical fractionation of intact, native complexes and correlation of protein profiles have shown promise. However, most approac...
Mass spectrometryProtein–protein interaction networksProteome informaticsProteomics
10.1038/S41592-021-01107-5
ISSN:1548-7091
NuFold: end-to-end approach for RNA tertiary structure prediction with flexible nucleobase center representation
Yuki Kagaya•Zicong Zhang•Nabil Ibtehaz•Xiao Wang•Tsukasa Nakamura等 7 人
Nature Communications
2025
•2025/1/21
•Vol.16 No.1 p.1-14
RNA plays a crucial role not only in information transfer as messenger RNA during gene expression but also in various biological functions as non-coding RNAs. Understanding mechanical mechanisms of function needs tertiary structure information; however, experimental determination of three-dimensiona...
Machine learningMolecular modellingProtein structure predictions
10.1038/S41467-025-56261-7
ISSN:2041-1723
Structural basis for intrinsic strand displacement activity of mitochondrial DNA polymerase
Ashok R. Nayak•Viktoriia Sokolova•Sirelin Sillamaa•Karl Herbine•Juhan Sedman等 6 人
Nature Communications
2025
•2025/3/11
•Vol.16 No.1 p.1-13
Members of the Pol A family of DNA polymerases, found across all domains of life, utilize various strategies for DNA strand separation during replication. In higher eukaryotes, mitochondrial DNA polymerase γ relies on the replicative helicase TWINKLE, whereas the yeast ortholog, Mip1, can unwind DNA...
Cryoelectron microscopyDNA synthesis
10.1038/S41467-025-57594-Z
ISSN:2041-1723
C–N bond formation by a polyketide synthase
Wang Jialiang•Wang Xiaojie•Li Xixi•Kong LiangLiang•Du Zeqian等 15 人
Nature Communications
2023
•2023/3/10
•Vol.14 No.1 p.1-14
Assembly-line polyketide synthases (PKSs) are molecular factories that produce diverse metabolites with wide-ranging biological activities. PKSs usually work by constructing and modifying the polyketide backbone successively. Here, we present the cryo-EM structure of CalA3, a chain release PKS modul...
BiocatalysisCryoelectron microscopyEnzyme mechanisms
10.1038/S41467-023-36989-W
ISSN:2041-1723
Common helical V1V2 conformations of HIV-1 Envelope expose the α4β7 binding site on intact virions
Constantinos Kurt Wibmer•Simone I. Richardson•Jason Yolitz•Claudia Cicala•James Arthos等 7 人
Nature Communications
2018
•2018/10/26
•Vol.9 No.1 p.1-14
The α4β7 integrin is a non-essential HIV-1 adhesion receptor, bound by the gp120 V1V2 domain, facilitating rapid viral dissemination into gut-associated lymphoid tissues. Antibodies blocking this interaction early in infection can improve disease outcome, and V1V2-targeted antibodies were correlated...
AntibodiesHIV infectionsVaccinesX-ray crystallography
10.1038/S41467-018-06794-X
ISSN:2041-1723
Structural basis of a small monomeric Clivia fluorogenic RNA with a large Stokes shift
Kaiyi Huang•Qianqian Song•Mengyue Fang•Deqiang Yao•Xin Shen等 10 人
Nature Chemical Biology
2024
•2024/5/30
•00 p.1-8
RNA-based fluorogenic modules have revolutionized the spatiotemporal localization of RNA molecules. Recently, a fluorophore named 5-((Z)-4-((2-hydroxyethyl)(methyl)amino)benzylidene)-3-methyl-2-((E)-styryl)-3,5-dihydro-4H-imidazol-4-one (NBSI), emitting in red spectrum, and its cognate aptamer named...
RNAX-ray crystallography
10.1038/S41589-024-01633-1
ISSN:1552-4450
Functional characterization of a PROTAC directed against BRAF mutant V600E
Ganna Posternak•Xiaojing Tang•Pierre Maisonneuve•Ting Jin•Hugo Lavoie等 31 人
Nature Chemical Biology
2020
•2020/8/10
•Vol.16 No.11 p.1170-1178
The RAF family kinases function in the RAS–ERK pathway to transmit signals from activated RAS to the downstream kinases MEK and ERK. This pathway regulates cell proliferation, differentiation and survival, enabling mutations in RAS and RAF to act as potent drivers of human cancers. Drugs targeting t...
EnzymesKinasesSmall molecules
10.1038/S41589-020-0609-7
ISSN:1552-4450
Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM
Antanasijevic Aleksandar•Sewall Leigh M.•Cottrell Christopher A.•Carnathan Diane G.•Jimenez Luis E.等 32 人
Nature Communications
2021
•2021/8/10
•Vol.12 No.1 p.1-17
Engineered ectodomain trimer immunogens based on BG505 envelope glycoprotein are widely utilized as components of HIV vaccine development platforms. In this study, we used rhesus macaques to evaluate the immunogenicity of several stabilized BG505 SOSIP constructs both as free trimers and presented o...
Cryoelectron microscopyProtein vaccinesStructural biology
10.1038/S41467-021-25087-4
ISSN:2041-1723
A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair
Diana van den Heuvel•Cornelia G. Spruijt•Román González-Prieto•Angela Kragten•Michelle T. Paulsen等 17 人
Nature Communications
2021
•2021/2/26
•Vol.12 No.1 p.1-19
Bulky DNA lesions in transcribed strands block RNA polymerase II (RNAPII) elongation and induce a genome-wide transcriptional arrest. The transcription-coupled repair (TCR) pathway efficiently removes transcription-blocking DNA lesions, but how transcription is restored in the genome following DNA r...
Nucleotide excision repairProtein–protein interaction networksTranscription
10.1038/S41467-021-21520-W
ISSN:2041-1723
Improving fragment-based ab initio protein structure assembly using low-accuracy contact-map predictions
Mortuza S. M.•Zheng Wei•Zhang Chengxin•Li Yang•Pearce Robin等 6 人
Nature Communications
2021
•2021/8/18
•Vol.12 No.1 p.1-12
Sequence-based contact prediction has shown considerable promise in assisting non-homologous structure modeling, but it often requires many homologous sequences and a sufficient number of correct contacts to achieve correct folds. Here, we developed a method, C-QUARK, that integrates multiple deep-l...
Machine learningProtein foldingProtein structure predictions
10.1038/S41467-021-25316-W
ISSN:2041-1723
Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights into the branch junction
Florian Fäßler•Georgi Dimchev•Victor-Valentin Hodirnau•William Wan•Florian K. M. Schur
Nature Communications
2020
•2020/12/22
•Vol.11 No.1 p.1-10
The actin-related protein (Arp)2/3 complex nucleates branched actin filament networks pivotal for cell migration, endocytosis and pathogen infection. Its activation is tightly regulated and involves complex structural rearrangements and actin filament binding, which are yet to be understood. Here, w...
ActinCryoelectron tomography
10.1038/S41467-020-20286-X
ISSN:2041-1723
Sensing of autoinducer-2 by functionally distinct receptors in prokaryotes
Lei Zhang•Shuyu Li•Xiaozhen Liu•Zhuo Wang•Mei Jiang等 16 人
Nature Communications
2020
•2020/10/23
•Vol.11 No.1 p.1-13
Autoinducer-2 (AI-2) is a quorum sensing signal that mediates communication within and between many bacterial species. However, its known receptors (LuxP and LsrB families) are not found in all the bacteria capable of responding to this signaling molecule. Here, we identify a third type of AI-2 rece...
BacteriaBiofilmsMicrobial communitiesExtracellular signalling molecules
10.1038/S41467-020-19243-5
ISSN:2041-1723
Rational design of next-generation filovirus vaccines combining glycoprotein stabilization and nanoparticle display with glycan modification
Yi-Zong Lee•Yi-Nan Zhang•Maddy L. Newby•Garrett Ward•Keegan Braz Gomes等 14 人
Nature Communications
2025
•2025/12/12
0Filoviruses pose a significant threat to human health due to frequent outbreaks and high mortality. Although two vector-based vaccines are available for Ebola virus, a broadly protective filovirus vaccine remains elusive. Here, we evaluate a general strategy for stabilizing glycoproteins (GP) from E...
Protein vaccines
10.1038/S41467-025-66367-7
ISSN:2041-1723
Generalizable mutation-effect prediction across adaptive immune recognition via unified multimodal framework
Rong Han•Yumeng Zhang•Xiaohong Liu•Lei Fu•Tong Pan等 17 人
Nature Machine Intelligence
2026
•2026/5/27
•00 p.1-17
Adaptive immunity is a central defence system essential for long-term and highly specific protection against pathogens through the precise molecular recognition of antigens by lymphocytes. However, predicting how mutations reshape these interactions remains a major challenge. Although previous compu...
Adaptive immunityComputational platforms and environmentsMachine learning
10.1038/S42256-026-01243-7
ISSN:2522-5839
Most azole resistance mutations in the Candida albicans drug target confer cross-resistance without intrinsic fitness cost
Camille Bédard•Isabelle Gagnon-Arsenault•Jonathan Boisvert•Samuel Plante•Alexandre K. Dubé等 11 人
Nature Microbiology
2024
•2024/10/8
•00 p.1-16
Azole antifungals are the main drugs used to treat fungal infections. Amino acid substitutions in the drug target Erg11 (Cyp51) are a common resistance mechanism in pathogenic yeasts. How many and which mutations confer resistance is, however, largely unknown. Here we measure the impact of nearly 4,...
Antifungal agentsHigh-throughput screening
10.1038/S41564-024-01819-2
ISSN:2058-5276
ScanNet: an interpretable geometric deep learning model for structure-based protein binding site prediction
Tubiana Jérôme•Schneidman-Duhovny Dina•Wolfson Haim J.
Nature Methods
2022
•2022/5/30
•00 p.1-10
Predicting the functional sites of a protein from its structure, such as the binding sites of small molecules, other proteins or antibodies, sheds light on its function in vivo. Currently, two classes of methods prevail: machine learning models built on top of handcrafted features and comparative mo...
Machine learningProtein function predictionsSoftware
10.1038/S41592-022-01490-7
ISSN:1548-7091
Sequence specificity analysis of the SETD2 protein lysine methyltransferase and discovery of a SETD2 super-substrate
Maren Kirstin Schuhmacher•Serap Beldar•Mina S. Khella•Alexander Bröhm•Jan Ludwig等 9 人
Communications Biology
2020
•2020/9/16
•Vol.3 No.1 p.1-13
SETD2 catalyzes methylation at lysine 36 of histone H3 and it has many disease connections. We investigated the substrate sequence specificity of SETD2 and identified nine additional peptide and one protein (FBN1) substrates. Our data showed that SETD2 strongly prefers amino acids different from tho...
Enzyme mechanismsMethylasesMethylationTransferasesX-ray crystallography
10.1038/S42003-020-01223-6
ISSN:2399-3642
Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM
Radamaker Lynn•Karimi-Farsijani Sara•Andreotti Giada•Baur Julian•Neumann Matthias等 18 人
Nature Communications
2021
•2021/11/5
•Vol.12 No.1 p.1-11
Systemic AL amyloidosis is a rare disease that is caused by the misfolding of immunoglobulin light chains (LCs). Potential drivers of amyloid formation in this disease are post-translational modifications (PTMs) and the mutational changes that are inserted into the LCs by somatic hypermutation. Here...
Cryoelectron microscopyCryoelectron tomographyProtein aggregationStructural biology
10.1038/S41467-021-26553-9
ISSN:2041-1723
An assessment of the cytochrome P450 2-hydroxyisoflavanone synthase (2-HIS) crystal structure
Thomas L. Poulos
Communications Biology
2026
•2026/5/26
•Vol.9 No.1 p.7160
Structural biologyX-ray crystallography
10.1038/S42003-026-10258-0
ISSN:2399-3642
Mechanism of genome instability mediated by human DNA polymerase mu misincorporation
Miao Guo•Yina Wang•Yuyue Tang•Zijing Chen•Jinfeng Hou等 12 人
Nature Communications
2021
•2021/6/18
•Vol.12 No.1 p.1-9
Pol μ is capable of performing gap-filling repair synthesis in the nonhomologous end joining (NHEJ) pathway. Together with DNA ligase, misincorporation of dGTP opposite the templating T by Pol μ results in a promutagenic T:G mispair, leading to genomic instability. Here, crystal structures and kinet...
DNA synthesisEnzyme mechanismsHydrolases
10.1038/S41467-021-24096-7
ISSN:2041-1723
Modulating TRADD to restore cellular homeostasis and inhibit apoptosis
Daichao Xu•Heng Zhao•Minzhi Jin•Hong Zhu•Bing Shan等 25 人
Nature
2020
•2020/9/23
•Vol.587 No.7832 p.133-138
Cell death in human diseases is often a consequence of disrupted cellular homeostasis. If cell death is prevented without restoring cellular homeostasis, it may lead to a persistent dysfunctional and pathological state. Although mechanisms of cell death have been thoroughly investigated1–3, it remai...
AutophagyCell death in the nervous systemNeurological disorders
10.1038/S41586-020-2757-Z
ISSN:0028-0836
CryoEM reveals that ribosomes in microsporidian spores are locked in a dimeric hibernating state
Mathew McLaren•Rebecca Conners•Michail N. Isupov•Patricia Gil-Díez•Lavinia Gambelli等 10 人
Nature Microbiology
2023
•2023/9/14
•00 p.1-12
Translational control is an essential process for the cell to adapt to varying physiological or environmental conditions. To survive adverse conditions such as low nutrient levels, translation can be shut down almost entirely by inhibiting ribosomal function. Here we investigated eukaryotic hibernat...
Cryoelectron microscopyCryoelectron tomographyImmunologyMechanisms of diseaseMicrobiology
10.1038/S41564-023-01469-W
ISSN:2058-5276
Deep learning large-scale drug discovery and repurposing
Min Yu•Weiming Li•Yunru Yu•Yu Zhao•Lizhi Xiao等 9 人
Nature Computational Science
2024
•2024/8/21
•00 p.1-15
Large-scale drug discovery and repurposing is challenging. Identifying the mechanism of action (MOA) is crucial, yet current approaches are costly and low-throughput. Here we present an approach for MOA identification by profiling changes in mitochondrial phenotypes. By temporally imaging mitochondr...
Cell biologyComputational modelsComputational scienceDrug discovery
10.1038/S43588-024-00679-4
ISSN:2662-8457
Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein
Seth J. Zost•Pavlo Gilchuk•Rita E. Chen•James Brett Case•Joseph X. Reidy等 31 人
Nature Medicine
2020
•2020/7/10
•Vol.26 No.9 p.1422-1427
Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we us...
AntibodiesSARS-CoV-2
10.1038/S41591-020-0998-X
ISSN:1078-8956
Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection
Yu Guo•Guangshun Zhang•Qi Yang•Xiaowei Xie•Yang Lu等 39 人
Nature Communications
2023
•2023/6/15
•Vol.14 No.1 p.1-16
The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid ...
AntibodiesCryoelectron microscopySARS-CoV-2
10.1038/S41467-023-39267-X
ISSN:2041-1723
Tandem intermolecular [4 + 2] cycloadditions are catalysed by glycosylated enzymes for natural product biosynthesis
Jiawang Liu•Jiayan Lu•Chen Zhang•Qingyang Zhou•Cooper S. Jamieson等 9 人
Nature Chemistry
2023
•2023/6/26
•00 p.1-8
Tandem Diels–Alder reactions are frequently used in the construction of polycyclic ring systems in complex organic compounds. Unlike the many Diels−Alderases (DAases) that catalyse a single cycloaddition, enzymes for multiple Diels–Alder reactions are rare. Here we demonstrate that two calcium-ion-d...
BiocatalysisBiosynthesisEnzyme mechanismsNatural products
10.1038/S41557-023-01260-8
ISSN:1755-4330
The atomic-resolution crystal structure of activated [Fe]-hydrogenase
Gangfeng Huang•Tristan Wagner•Matthew D. Wodrich•Kenichi Ataka•Eckhard Bill等 8 人
Nature Catalysis
2019
•2019/6/10
•Vol.2 No.6 p.537-543
Hydrogenases are promising templates for constructing new H2-based catalysts. [Fe]-hydrogenase, which features an iron-guanylylpyridinol (FeGP) cofactor, catalyses a reversible hydride transfer from H2 to methenyl-tetrahydromethanopterin (methenyl-H4MPT+, a C1 carrier in methanogens). Here, we prese...
BiocatalysisEnzyme mechanismsMetalloproteinsOxidoreductasesX-ray crystallography
10.1038/S41929-019-0289-4
ISSN:2520-1158
Bifunctionality of dirhodium tetracarboxylates in metallaphotocatalysis
Taoda Shi•Tianyuan Zhang•Jiying Yang•Yukai Li•Jirong Shu等 9 人
Nature Communications
2023
•2023/11/10
•Vol.14 No.1 p.1-10
Metallaphotocatalysis has been recognized as a pivotal catalysis enabling new reactivities. Traditional metallaphotocatalysis often requires two or more separate catalysts and exhibits flaw in cost and substrate-tolerance, thus representing an await-to-solve issue in catalysis. We herein realize met...
Drug discovery and developmentHomogeneous catalysisSynthetic chemistry methodology
10.1038/S41467-023-43050-3
ISSN:2041-1723
CryoEM structures reveal how the bacterial flagellum rotates and switches direction
Prashant K. Singh•Pankaj Sharma•Oshri Afanzar•Margo H. Goldfarb•Elena Maklashina等 8 人
Nature Microbiology
2024
•2024/4/17
•00 p.1-11
Bacterial chemotaxis requires bidirectional flagellar rotation at different rates. Rotation is driven by a flagellar motor, which is a supercomplex containing multiple rings. Architectural uncertainty regarding the cytoplasmic C-ring, or ‘switch’, limits our understanding of how the motor transmits ...
BacteriaCryoelectron microscopy
10.1038/S41564-024-01674-1
ISSN:2058-5276
A highly active Burkholderia polyketoacyl-CoA thiolase for production of triacetic acid lactone
Zilong Wang•Seokjung Cheong•Jose Henrique Pereira•Weixi Hu•Yifan Guo等 12 人
Nature Communications
2025
•2025/12/9
•Vol.16 No.1 p.109900
Triacetic acid lactone (TAL) is a versatile platform chemical traditionally biosynthesized via decarboxylative Claisen condensation by 2-pyrone synthase. However, this route is limited by poor efficiency and dependence on malonyl-CoA. Here, we show that non-decarboxylative Claisen condensation by po...
Applied microbiologyBiocatalysisMetabolic engineeringSynthetic biology
10.1038/S41467-025-65946-Y
ISSN:2041-1723
Towards a molecular picture of the archaeal cell surface
Matthew C. Gaines•Michail N. Isupov•Mathew McLaren•Clara L. Mollat•Risat Ul Haque等 12 人
Nature Communications
2024
•2024/11/29
•Vol.15 No.1 p.1-16
Archaea produce various protein filaments with specialised functions. While some archaea produce only one type of filament, the archaeal model species Sulfolobus acidocaldarius generates four. These include rotary swimming propellers analogous to bacterial flagella (archaella), pili for twitching mo...
Archaeal biologyCellular microbiologyCryoelectron microscopy
10.1038/S41467-024-53986-9
ISSN:2041-1723
Structures of TRPV2 in distinct conformations provide insight into role of the pore turret
Timothy L. Dosey•Zhao Wang•Guizhen Fan•Zhixian Zhang•Irina I. Serysheva等 7 人
Nature Structural & Molecular Biology
2018
•2018/12/31
•Vol.26 No.1 p.40-49
Cation channels of the transient receptor potential (TRP) family serve important physiological roles by opening in response to diverse intra- and extracellular stimuli that regulate their lower or upper gates. Despite extensive studies, the mechanism coupling these gates has remained obscure. Previo...
Cryoelectron microscopyMembrane proteinsTransient receptor potential channels
10.1038/S41594-018-0168-8
ISSN:1545-9993
Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3
Jark Böttcher•David Dilworth•Ulrich Reiser•Ralph A. Neumüller•Michael Schleicher等 44 人
Nature Chemical Biology
2019
•2019/7/8
•Vol.15 No.8 p.822-829
Here, we report the fragment-based discovery of BI-9321, a potent, selective and cellular active antagonist of the NSD3-PWWP1 domain. The human NSD3 protein is encoded by the WHSC1L1 gene located in the 8p11-p12 amplicon, frequently amplified in breast and squamous lung cancer. Recently, it was demo...
CancerChemical biologyDrug discoveryStructural biologyStructure-based drug design
10.1038/S41589-019-0310-X
ISSN:1552-4450
De novo design of protein minibinder agonists of TLR3
Chloe S. Adams•Hyojin Kim•Abigail E. Burtner•Dong Sun Lee•Craig Dobbins等 10 人
Nature Communications
2025
•2025/1/31
•Vol.16 No.1 p.1-11
Toll-like Receptor 3 (TLR3) is a pattern recognition receptor that initiates antiviral immune responses upon binding double-stranded RNA (dsRNA). Several nucleic acid-based TLR3 agonists have been explored clinically as vaccine adjuvants in cancer and infectious disease, but present substantial manu...
Cryoelectron microscopyProtein designToll-like receptors
10.1038/S41467-025-56369-W
ISSN:2041-1723
A structural basis for prion strain diversity
Manka Szymon W.•Wenborn Adam•Betts Jemma•Joiner Susan•Saibil Helen R.等 7 人
Nature Chemical Biology
2023
•2023/1/16
•00 p.1-7
Recent cryogenic electron microscopy (cryo-EM) studies of infectious, ex vivo, prion fibrils from hamster 263K and mouse RML prion strains revealed a similar, parallel in-register intermolecular β-sheet (PIRIBS) amyloid architecture. Rungs of the fibrils are composed of individual prion protein (PrP...
Neurodegenerative diseasesProtein aggregationStructure determination
10.1038/S41589-022-01229-7
ISSN:1552-4450
Protein identification by 3D OrbiSIMS to facilitate in situ imaging and depth profiling
Anna M. Kotowska•Gustavo F. Trindade•Paula M. Mendes•Philip M. Williams•Jonathan W. Aylott等 8 人
Nature Communications
2020
•2020/11/17
•Vol.11 No.1 p.1-8
Label-free protein characterization at surfaces is commonly achieved using digestion and/or matrix application prior to mass spectrometry. We report the assignment of undigested proteins at surfaces in situ using secondary ion mass spectrometry (SIMS). Ballistic fragmentation of proteins induced by ...
Mass spectrometryMolecular imagingProteins
10.1038/S41467-020-19445-X
ISSN:2041-1723
Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies
Renhong Yan•Ruoke Wang•Bin Ju•Jinfang Yu•Yuanyuan Zhang等 25 人
Cell Research
2021
•2021/3/17
•00 p.1-9
Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disruptin...
Cryoelectron microscopyMechanisms of disease
10.1038/S41422-021-00487-9
ISSN:1001-0602
Targeted cross-linker delivery for the in situ mapping of protein conformations and interactions in mitochondria
Yuwan Chen•Wen Zhou•Yufei Xia•Weijie Zhang•Qun Zhao等 12 人
Nature Communications
2023
•2023/6/30
•Vol.14 No.1 p.1-16
Current methods for intracellular protein analysis mostly require the separation of specific organelles or changes to the intracellular environment. However, the functions of proteins are determined by their native microenvironment as they usually form complexes with ions, nucleic acids, and other p...
Cell deliveryMitochondrial proteinsProtein–protein interaction networksProtein structure predictionsProteomics
10.1038/S41467-023-39485-3
ISSN:2041-1723
Cross-regulation of [2Fe–2S] cluster synthesis by ferredoxin-2 and frataxin
Kristian Want•Hubert Gorny•Ema Turki•Magali Noiray•Beata Monfort等 10 人
Nature
2025
•2025/12/10
•00 p.1-8
Iron–sulfur (Fe–S) clusters are essential metallocofactors that perform a multitude of biological functions1–7. Their synthesis is tightly regulated and defects in this process lead to severe diseases8–10, such as Friedreich’s ataxia, which is caused by defective expression of frataxin (FXN)11. Howe...
Enzyme mechanismsIron
10.1038/S41586-025-09822-1
ISSN:0028-0836
Cryo-EM structure of the yeast Saccharomyces cerevisiae SDH provides a template for eco-friendly fungicide discovery
Zhi-Wen Li•Yuan-Hui Huang•Ge Wei•Zong-Wei Lu•Yu-Xia Wang等 14 人
Nature Communications
2025
•2025/10/8
•Vol.16 No.1 p.1-13
Succinate dehydrogenase (SDH) is a key fungicidal target, but rational inhibitors design has been impeded by the lack of fungal SDH structure. Here, we show the cryo-EM structure of SDH from Saccharomyces cerevisiae (ScSDH) in apo (3.36 Å) and ubiquinone-1-bound (3.25 Å) states, revealing subunits a...
Cryoelectron microscopyEnzymesProteins
10.1038/S41467-025-64001-0
ISSN:2041-1723
Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover
Kelli L. Hvorecny•Thomas E. Sladewski•Enrique M. De La Cruz•Justin M. Kollman•Aoife T. Heaslip
Nature Communications
2024
•2024/2/28
•Vol.15 No.1 p.1-16
The cytoskeletal protein actin plays a critical role in the pathogenicity of the intracellular parasite, Toxoplasma gondii, mediating invasion and egress, cargo transport, and organelle inheritance. Advances in live cell imaging have revealed extensive filamentous actin networks in the Apicomplexan ...
Cryoelectron microscopyMolecular biophysicsParasite biology
10.1038/S41467-024-46111-3
ISSN:2041-1723
A dual diffusion model enables 3D molecule generation and lead optimization based on target pockets
Lei Huang•Tingyang Xu•Yang Yu•Peilin Zhao•Xingjian Chen等 11 人
Nature Communications
2024
•2024/3/26
•Vol.15 No.1 p.1-16
Structure-based generative chemistry is essential in computer-aided drug discovery by exploring a vast chemical space to design ligands with high binding affinity for targets. However, traditional in silico methods are limited by computational inefficiency, while machine learning approaches face bot...
Computational modelsDrug discoveryDrug screeningProtein design
10.1038/S41467-024-46569-1
ISSN:2041-1723
Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer
Xiaocui Lu•Xiuyun Wang•Zheng Yang•Xusheng Wang•Lin Wang等 21 人
Nature
2026
•2026/6/10
•00 p.1-10
BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerizat...
Targeted therapies
10.1038/S41586-026-10613-5
ISSN:0028-0836
Enzymatic β-elimination in natural product O- and C-glycoside deglycosylation
Johannes Bitter•Martin Pfeiffer•Annika J. E. Borg•Kirill Kuhlmann•Tea Pavkov-Keller等 7 人
Nature Communications
2023
•2023/11/6
•Vol.14 No.1 p.1-17
Biological degradation of natural product glycosides involves, alongside hydrolysis, β-elimination for glycosidic bond cleavage. Here, we discover an O-glycoside β-eliminase (OGE) from Agrobacterium tumefaciens that converts the C3-oxidized O-β-d-glucoside of phloretin (a plant-derived flavonoid) in...
BiocatalysisEnzyme mechanismsEnzymesGlycosidesX-ray crystallography
10.1038/S41467-023-42750-0
ISSN:2041-1723
Biased localization of actin binding proteins by actin filament conformation
Andrew R. Harris•Pamela Jreij•Brian Belardi•Aaron M. Joffe•Andreas R. Bausch等 6 人
Nature Communications
2020
•2020/11/25
•Vol.11 No.1 p.1-13
The assembly of actin filaments into distinct cytoskeletal structures plays a critical role in cell physiology, but how proteins localize differentially to these structures within a shared cytoplasm remains unclear. Here, we show that the actin-binding domains of accessory proteins can be sensitive ...
ActinCell migrationKineticsSingle-molecule biophysicsSuper-resolution microscopy
10.1038/S41467-020-19768-9
ISSN:2041-1723
Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome
Bengi Ruken Yavuz•M. Kaan Arici•Habibe Cansu Demirel•Chung-Jung Tsai•Hyunbum Jang等 7 人
Npj Genomic Medicine
2023
•2023/11/4
•Vol.8 No.1 p.1-14
Epidemiological studies suggest that individuals with neurodevelopmental disorders (NDDs) are more prone to develop certain types of cancer. Notably, however, the case statistics can be impacted by late discovery of cancer in individuals afflicted with NDDs, such as intellectual disorders, autism, a...
Computational biology and bioinformaticsSystems biology
10.1038/S41525-023-00377-6
ISSN:2056-7944
Nucleotide-induced hyper-oligomerization inactivates transcription termination factor ρ
Bing Wang•Nelly Said•Tarek Hilal•Mark Finazzo•Markus C. Wahl等 6 人
Nature Communications
2025
•2025/2/15
•Vol.16 No.1 p.1-16
Bacterial RNA helicase ρ is a genome sentinel that terminates the synthesis of damaged and junk RNAs that are not translated by the ribosome. It is unclear how ρ is regulated during dormancy or stress, when translation is inefficient and RNAs are vulnerable to ρ-mediated release. We use cryogenic el...
Cryoelectron microscopyMicrobiologyTranscriptional regulatory elements
10.1038/S41467-025-56824-8
ISSN:2041-1723
Decoding the functional impact of the cancer genome through protein–protein interactions
Haian Fu•Xiulei Mo•Andrey A. Ivanov
Nature Reviews Cancer
2025
•2025/1/14
•00 p.1-20
Acquisition of genomic mutations enables cancer cells to gain fitness advantages under selective pressure and, ultimately, leads to oncogenic transformation. Interestingly, driver mutations, even within the same gene, can yield distinct phenotypes and clinical outcomes, necessitating a mutation-focu...
Cancer genomicsOncogenesTarget identificationTumour-suppressor proteins
10.1038/S41568-024-00784-6
ISSN:1474-175X
Actinomycetes-derived imine reductases with a preference towards bulky amine substrates
Zhang Jun•Li Xin•Chen Rongchang•Tan Xianwei•Liu Xiongduo等 17 人
Communications Chemistry
2022
•2022/10/8
•Vol.5 No.1 p.1-9
Since imine reductases (IREDs) were reported to catalyze the reductive amination reactions, they became particularly attractive for producing chiral amines. Though diverse ketones and aldehydes have been proved to be excellent substrates of IREDs, bulky amines have been rarely transformed. Here we r...
BiocatalysisEnzymes
10.1038/S42004-022-00743-Y
ISSN:2399-3669
Molecular basis of potent antiviral HLA-C-restricted CD8+ T cell response to an immunodominant SARS-CoV-2 nucleocapsid epitope
Yoshihiko Goto•You Min Ahn•Mako Toyoda•Hiroshi Hamana•Yan Jin等 27 人
Nature Communications
2025
•2025/8/28
•Vol.16 No.1 p.1-18
The emergence of SARS-CoV-2 Variants of Concern (VOC) is a major clinical threat; however, VOC remain susceptible to cytotoxic T lymphocyte (CTL) recognition. Therefore, it is crucial to identify potent CTL responses targeting conserved epitopes across VOCs. Here, we demonstrate that the nucleocapsi...
Cytotoxic T cellsImmunological memorySARS-CoV-2Viral infection
10.1038/S41467-025-63288-3
ISSN:2041-1723
Structure-function analysis of carrier protein-dependent 2-sulfamoylacetyl transferase in the biosynthesis of altemicidin
Yuhao Zhu•Takahiro Mori•Masayuki Karasawa•Kohei Shirai•Wenjiao Cheng等 8 人
Nature Communications
2024
•2024/12/30
•Vol.15 No.1 p.1-13
The general control non-repressible 5 (GCN5)-related N-acetyltransferase (GNAT) SbzI, in the biosynthesis of the sulfonamide antibiotic altemicidin, catalyzes the transfer of the 2-sulfamoylacetyl (2-SA) moiety onto 6-azatetrahydroindane dinucleotide. While most GNAT superfamily utilize acyl-coenzym...
Computational biophysicsEnzyme mechanismsMolecular biophysicsX-ray crystallography
10.1038/S41467-024-55265-Z
ISSN:2041-1723
Uncovering bacterial pseudaminylation with pan-specific antibody tools
Arthur H. Tang•Niccolay Madiedo Soler•Kristian I. Karlic•Leo Corcilius•Caitlin E. Clarke-Shepperson等 32 人
Nature Chemical Biology
2026
•2026/2/4
•Vol.22 No.4 p.622-633
Pseudaminic acids (Pse) are a family of carbohydrates found within bacterial lipopolysaccharides, capsular polysaccharides and glycoproteins that are critical for the virulence of human pathogens. However, a dearth of effective tools for detecting and enriching Pse has restricted study to only the m...
BacteriaCarbohydratesGlycobiology
10.1038/S41589-025-02114-9
ISSN:1552-4450
The structure of the teleost Immunoglobulin M core provides insights on polymeric antibody evolution, assembly, and function
Mengfan Lyu•Andrey G. Malyutin•Beth M. Stadtmueller
Nature Communications
2023
•2023/11/21
•Vol.14 No.1 p.1-14
Polymeric (p) immunoglobulins (Igs) serve broad functions during vertebrate immune responses. Typically, pIgs contain between two and six Ig monomers, each with two antigen binding fragments and one fragment crystallization (Fc). In addition, many pIgs assemble with a joining-chain (JC); however, th...
AntibodiesCryoelectron microscopyImmunogenetics
10.1038/S41467-023-43240-Z
ISSN:2041-1723
Structure and catalytic activity of the SAM-utilizing ribozyme SAMURI
Hsuan-Ai Chen•Takumi Okuda•Ann-Kathrin Lenz•Carolin P. M. Scheitl•Hermann Schindelin等 6 人
Nature Chemical Biology
2025
•2025/1/8
•00 p.1-10
Ribozymes that catalyze site-specific RNA modification have recently gained increasing interest for their ability to mimic methyltransferase enzymes and for their application to install molecular tags. Recently, we reported SAMURI as a site-specific alkyltransferase ribozyme using S-adenosylmethioni...
RNAX-ray crystallography
10.1038/S41589-024-01808-W
ISSN:1552-4450
Alkaloid binding to opium poppy major latex proteins triggers structural modification and functional aggregation
Ozber Natali•Carr Samuel C.•Morris Jeremy S.•Liang Siyu•Watkins Jacinta L.等 9 人
Nature Communications
2022
•2022/11/9
•Vol.13 No.1 p.1-16
Opium poppy accumulates copious amounts of several benzylisoquinoline alkaloids including morphine, noscapine, and papaverine, in the specialized cytoplasm of laticifers, which compose an internal secretory system associated with phloem throughout the plant. The contiguous latex includes an abundanc...
Plant cell biologySecondary metabolismX-ray crystallography
10.1038/S41467-022-34313-6
ISSN:2041-1723
Accurate prediction of protein–nucleic acid complexes using RoseTTAFoldNA
Minkyung Baek•Ryan McHugh•Ivan Anishchenko•Hanlun Jiang•David Baker等 6 人
Nature Methods
2023
•2023/11/23
•00 p.1-5
Protein–RNA and protein–DNA complexes play critical roles in biology. Despite considerable recent advances in protein structure prediction, the prediction of the structures of protein–nucleic acid complexes without homology to known complexes is a largely unsolved problem. Here we extend the RoseTTA...
DNA-binding proteinsMachine learningRNA-binding proteins
10.1038/S41592-023-02086-5
ISSN:1548-7091
Novel tau filament fold in corticobasal degeneration
Wenjuan Zhang•Airi Tarutani•Kathy L. Newell•Alexey G. Murzin•Tomoyasu Matsubara等 15 人
Nature
2020
•2020/2/12
•Vol.580 No.7802 p.283-287
Corticobasal degeneration (CBD) is a neurodegenerative tauopathy—a class of disorders in which the tau protein forms insoluble inclusions in the brain—that is characterized by motor and cognitive disturbances1–3. The H1 haplotype of MAPT (the tau gene) is present in cases of CBD at a higher frequenc...
Cryoelectron microscopyNeurodegeneration
10.1038/S41586-020-2043-0
ISSN:0028-0836
Structural basis for modulation of human NaV1.3 by clinical drug and selective antagonist
Li Xiaojing•Xu Feng•Xu Hao•Zhang Shuli•Gao Yiwei等 13 人
Nature Communications
2022
•2022/3/11
•Vol.13 No.1 p.1-10
Voltage-gated sodium (NaV) channels play fundamental roles in initiating and propagating action potentials. NaV1.3 is involved in numerous physiological processes including neuronal development, hormone secretion and pain perception. Here we report structures of human NaV1.3/β1/β2 in complex with cl...
Cryoelectron microscopyIon transportMembrane proteinsSodium channels
10.1038/S41467-022-28808-5
ISSN:2041-1723
Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2
Sun Shihui•Gu Hongjing•Cao Lei•Chen Qi•Ye Qing等 30 人
Nature Communications
2021
•2021/9/27
•Vol.12 No.1 p.1-16
There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep...
PathogensSARS-CoV-2Structural biologyVirus–host interactions
10.1038/S41467-021-25903-X
ISSN:2041-1723
Structural insights into the human HRD1 ubiquitin ligase complex
Liling Guo•Guoyun Liu•Jingjing He•Xiaoxiao Jia•Yonglin He等 7 人
Nature Communications
2025
•2025/7/1
•Vol.16 No.1 p.1-12
In the endoplasmic reticulum (ER), defective proteins are cleaned via the ER-associated protein degradation (ERAD) pathway. The HRD1 ubiquitin ligase complex, with HRD1, SEL1L, XTP3B or OS9 and Derlin family proteins as the core components, plays essential roles in the recognition, retrotranslocatio...
Cryoelectron microscopyER-associated degradation
10.1038/S41467-025-61143-Z
ISSN:2041-1723
Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail
Dong Jinhui•Zost Seth J.•Greaney Allison J.•Starr Tyler N.•Dingens Adam S.等 32 人
Nature Microbiology
2021
•2021/9/21
•00 p.1-12
Understanding the molecular basis for immune recognition of SARS-CoV-2 spike glycoprotein antigenic sites will inform the development of improved therapeutics. We determined the structures of two human monoclonal antibodies–AZD8895 and AZD1061–which form the basis of the investigational antibody coc...
SARS-CoV-2Viral infection
10.1038/S41564-021-00972-2
ISSN:2058-5276
An enzymatic activation of formaldehyde for nucleotide methylation
Bou-Nader Charles•Stull Frederick W.•Pecqueur Ludovic•Simon Philippe•Guérineau Vincent等 10 人
Nature Communications
2021
•2021/7/27
•Vol.12 No.1 p.1-8
Folate enzyme cofactors and their derivatives have the unique ability to provide a single carbon unit at different oxidation levels for the de novo synthesis of amino-acids, purines, or thymidylate, an essential DNA nucleotide. How these cofactors mediate methylene transfer is not fully settled yet,...
Enzyme mechanismsX-ray crystallography
10.1038/S41467-021-24756-8
ISSN:2041-1723
DiffModeler: large macromolecular structure modeling for cryo-EM maps using a diffusion model
Xiao Wang•Han Zhu•Genki Terashi•Manav Taluja•Daisuke Kihara
Nature Methods
2024
•2024/10/21
•00 p.1-11
Cryogenic electron microscopy (cryo-EM) has now been widely used for determining multichain protein complexes. However, modeling a large complex structure, such as those with more than ten chains, is challenging, particularly when the map resolution decreases. Here we present DiffModeler, a fully au...
Molecular biophysicsProtein structure predictions
10.1038/S41592-024-02479-0
ISSN:1548-7091
Signaling by a bacterial phytochrome histidine kinase involves a conformational cascade reorganizing the dimeric photoreceptor
E. Sethe Burgie•Katherine Basore•Michael J. Rau•Brock Summers•Alayna J. Mickles等 8 人
Nature Communications
2024
•2024/8/10
•Vol.15 No.1 p.1-16
Phytochromes (Phys) are a divergent cohort of bili-proteins that detect light through reversible interconversion between dark-adapted Pr and photoactivated Pfr states. While our understandings of downstream events are emerging, it remains unclear how Phys translate light into an interpretable confor...
Cryoelectron microscopyKinasesMolecular conformationProtein structure predictions
10.1038/S41467-024-50412-Y
ISSN:2041-1723
Autoantibody binding and unique enzyme-substrate intermediate conformation of human transglutaminase 3
Julie Elisabeth Heggelund•Saykat Das•Jorunn Stamnaes•Rasmus Iversen•Ludvig M. Sollid
Nature Communications
2023
•2023/10/5
•Vol.14 No.1 p.1-11
Transglutaminase 3 (TG3), the autoantigen of dermatitis herpetiformis (DH), is a calcium dependent enzyme that targets glutamine residues in polypeptides for either transamidation or deamidation modifications. To become catalytically active TG3 requires proteolytic cleavage between the core domain a...
AutoimmunityEnzymesX-ray crystallography
10.1038/S41467-023-42004-Z
ISSN:2041-1723
Combinatorial expression of GPCR isoforms affects signalling and drug responses
Maria Marti-Solano•Stephanie E. Crilly•Duccio Malinverni•Christian Munk•Matthew Harris等 16 人
Nature
2020
•2020/11/4
•Vol.587 No.7835 p.650-656
G-protein-coupled receptors (GPCRs) are membrane proteins that modulate physiology across human tissues in response to extracellular signals. GPCR-mediated signalling can differ because of changes in the sequence1,2 or expression3 of the receptors, leading to signalling bias when comparing diverse p...
Computational biology and bioinformaticsSystems biology
10.1038/S41586-020-2888-2
ISSN:0028-0836
Integrating end-to-end learning with deep geometrical potentials for ab initio RNA structure prediction
Yang Li•Chengxin Zhang•Chenjie Feng•Robin Pearce•P. Lydia Freddolino等 6 人
Nature Communications
2023
•2023/9/16
•Vol.14 No.1 p.1-13
RNAs are fundamental in living cells and perform critical functions determined by their tertiary architectures. However, accurate modeling of 3D RNA structure remains a challenging problem. We present a novel method, DRfold, to predict RNA tertiary structures by simultaneous learning of local frame ...
Computational modelsMachine learning
10.1038/S41467-023-41303-9
ISSN:2041-1723
DNA topoisomerase I acts as supercoiling sensor for bacterial transcription elongation
Vita Vidmar•Céline Borde•Lisa Bruno•Nataliya Miropolskaya•Maria Takacs等 11 人
Nature Structural & Molecular Biology
2025
•2025/12/1
•Vol.33 No.1 p.134-144
During transcription, RNA polymerase (RNAP) continuously unwinds and rewinds DNA, generating negative and positive supercoils upstream and downstream, respectively. Using single-particle cryo-EM, we elucidated how bacterial RNAP and DNA topoisomerase I (TopoI), which relaxes negative supercoils, ope...
Cryoelectron microscopyDNAEnzyme mechanismsGenomicsRNA
10.1038/S41594-025-01703-5
ISSN:1545-9993
Exploring ligand binding pathways on proteins using hypersound-accelerated molecular dynamics
Mitsugu Araki•Shigeyuki Matsumoto•Gert-Jan Bekker•Yuta Isaka•Yukari Sagae等 7 人
Nature Communications
2021
•2021/5/14
•Vol.12 No.1 p.1-10
Capturing the dynamic processes of biomolecular systems in atomistic detail remains difficult despite recent experimental advances. Although molecular dynamics (MD) techniques enable atomic-level observations, simulations of “slow” biomolecular processes (with timescales longer than submilliseconds)...
Computational biophysicsDrug developmentSingle-molecule biophysics
10.1038/S41467-021-23157-1
ISSN:2041-1723
Accelerated rational PROTAC design via deep learning and molecular simulations
Zheng Shuangjia•Tan Youhai•Wang Zhenyu•Li Chengtao•Zhang Zhiqing等 8 人
Nature Machine Intelligence
2022
•2022/9/15
•Vol.4 No.9 p.739-748
Proteolysis-targeting chimeras (PROTACs) have emerged as effective tools to selectively degrade disease-related proteins by using the ubiquitin-proteasome system. Developing PROTACs involves extensive tests and trials to explore the vast chemical space. To accelerate this process, we propose a novel...
Computational chemistryMachine learningVirtual drug screening
10.1038/S42256-022-00527-Y
ISSN:2522-5839
Allomorphy as a mechanism of post-translational control of enzyme activity
Henry P. Wood•F. Aaron Cruz-Navarrete•Nicola J. Baxter•Clare R. Trevitt•Angus J. Robertson等 9 人
Nature Communications
2020
•2020/11/2
•Vol.11 No.1 p.1-12
Enzyme regulation is vital for metabolic adaptability in living systems. Fine control of enzyme activity is often delivered through post-translational mechanisms, such as allostery or allokairy. β-phosphoglucomutase (βPGM) from Lactococcus lactis is a phosphoryl transfer enzyme required for complete...
BiocatalysisEnzyme mechanismsMolecular conformationSolution-state NMRX-ray crystallography
10.1038/S41467-020-19215-9
ISSN:2041-1723
A soybean cyst nematode suppresses microbial plant symbionts using a lipochitooligosaccharide-hydrolysing enzyme
Wei Chen•Di Wang•Shaoyong Ke•Yangrong Cao•Wensheng Xiang等 7 人
Nature Microbiology
2024
•2024/6/17
•00 p.1-13
Cyst nematodes are the most damaging species of plant-parasitic nematodes. They antagonize the colonization of beneficial microbial symbionts that are important for nutrient acquisition of plants. The molecular mechanism of the antagonism, however, remains elusive. Here, through biochemical combined...
Arbuscular mycorrhizaParasitismRhizobial symbiosis
10.1038/S41564-024-01727-5
ISSN:2058-5276
Par complex cluster formation mediated by phase separation
Ziheng Liu•Ying Yang•Aihong Gu•Jiawen Xu•Ying Mao等 12 人
Nature Communications
2020
•2020/5/8
•Vol.11 No.1 p.1-18
The evolutionarily conserved Par3/Par6/aPKC complex regulates the polarity establishment of diverse cell types and distinct polarity-driven functions. However, how the Par complex is concentrated beneath the membrane to initiate cell polarization remains unclear. Here we show that the Par complex ex...
BiochemistryBiophysicsCell divisionCell polarityNeurogenesis
10.1038/S41467-020-16135-6
ISSN:2041-1723
Structural insights into Ubr1-mediated N-degron polyubiquitination
Pan Man•Zheng Qingyun•Wang Tian•Liang Lujun•Mao Junxiong等 13 人
Nature
2021
•2021/11/17
•00 p.1-5
The N-degron pathway targets proteins that bear a destabilizing residue at the N terminus for proteasome-dependent degradation1. In yeast, Ubr1—a single-subunit E3 ligase—is responsible for the Arg/N-degron pathway2. How Ubr1 mediates the initiation of ubiquitination and the elongation of the ubiqui...
Cryoelectron microscopyEnzyme mechanismsUbiquitin ligasesUbiquitylation
10.1038/S41586-021-04097-8
ISSN:0028-0836
Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1
Hisano Yajima•Yuki Anraku•Yu Kaku•Kanako Terakado Kimura•Arnon Plianchaisuk等 18 人
Nature Communications
2024
•2024/10/7
•Vol.15 No.1 p.1-14
Since 2019, SARS-CoV-2 has undergone mutations, resulting in pandemic and epidemic waves. The SARS-CoV-2 spike protein, crucial for cellular entry, binds to the ACE2 receptor exclusively when its receptor-binding domain (RBD) adopts the up-conformation. However, whether ACE2 also interacts with the ...
Cryoelectron microscopySARS-CoV-2Virus structures
10.1038/S41467-024-52808-2
ISSN:2041-1723
Basis of the H2AK119 specificity of the Polycomb repressive deubiquitinase
Ge Weiran•Yu Cong•Li Jingjing•Yu Zhenyu•Li Xiaorong等 13 人
Nature
2023
•2023/3/29
•Vol.616 No.7955 p.176-182
Repression of gene expression by protein complexes of the Polycomb group is a fundamental mechanism that governs embryonic development and cell-type specification1–3. The Polycomb repressive deubiquitinase (PR-DUB) complex removes the ubiquitin moiety from monoubiquitinated histone H2A K119 (H2AK119...
Electron microscopyEpigenetics
10.1038/S41586-023-05841-Y
ISSN:0028-0836
Formation of thyroid hormone revealed by a cryo-EM structure of native bovine thyroglobulin
Marechal Nils•Serrano Banyuhay P.•Zhang Xinyan•Weitz Charles J.
Nature Communications
2022
•2022/5/2
•Vol.13 No.1 p.1-7
Thyroid hormones are essential regulators of metabolism, development, and growth. They are formed from pairs of iodinated tyrosine residues within the precursor thyroglobulin (TG), a 660-kDa homodimer of the thyroid gland, by an oxidative coupling reaction. Tyrosine pairs that give rise to thyroid h...
Cryoelectron microscopyThyroid hormones
10.1038/S41467-022-30082-4
ISSN:2041-1723
Dual domain recognition determines SARS-CoV-2 PLpro selectivity for human ISG15 and K48-linked di-ubiquitin
Wydorski Pawel M.•Osipiuk Jerzy•Lanham Benjamin T.•Tesar Christine•Endres Michael等 13 人
Nature Communications
2023
•2023/4/25
•Vol.14 No.1 p.1-18
The Papain-like protease (PLpro) is a domain of a multi-functional, non-structural protein 3 of coronaviruses. PLpro cleaves viral polyproteins and posttranslational conjugates with poly-ubiquitin and protective ISG15, composed of two ubiquitin-like (UBL) domains. Across coronaviruses, PLpro showed ...
Molecular modellingNMR spectroscopyProteasesX-ray crystallography
10.1038/S41467-023-38031-5
ISSN:2041-1723
Assembly and gating mechanism of native AMPA receptors from the cerebellum
Xiaojing Li•Renjie Li•Yiqing Wei•Jiexin Chen•Jiaojiao Zhao等 17 人
Cell Research
2026
•2026/3/16
•00 p.1-14
AMPA receptors (AMPARs) mediate the majority of fast excitatory synaptic transmission throughout the central nervous system. Calcium-permeable AMPARs and GluA4-containing receptors are critical for cerebellar functions, such as motor learning, associative memory, auditory processing, and synaptic pl...
Cryoelectron microscopyProtein folding
10.1038/S41422-026-01234-8
ISSN:1748-7838
Structural basis for hepatitis B virus restriction by a viral receptor homologue
Kaho Shionoya•Jae-Hyun Park•Toru Ekimoto•Junko S. Takeuchi•Junki Mifune等 18 人
Nature Communications
2024
•2024/10/25
•Vol.15 No.1 p.1-15
Macaque restricts hepatitis B virus (HBV) infection because its receptor homologue, NTCP (mNTCP), cannot bind preS1 on viral surface. To reveal how mNTCP loses the viral receptor function, we here solve the cryo-electron microscopy structure of mNTCP. Superposing on the human NTCP (hNTCP)-preS1 comp...
Cryoelectron microscopyHepatitis B virus
10.1038/S41467-024-53533-6
ISSN:2041-1723
The HaloTag as a general scaffold for far-red tunable chemigenetic indicators
Claire Deo•Ahmed S. Abdelfattah•Hersh K. Bhargava•Adam J. Berro•Natalie Falco等 10 人
Nature Chemical Biology
2021
•2021/4/1
•00 p.1-6
Functional imaging using fluorescent indicators has revolutionized biology, but additional sensor scaffolds are needed to access properties such as bright, far-red emission. Here, we introduce a new platform for ‘chemigenetic’ fluorescent indicators, utilizing the self-labeling HaloTag protein conju...
Chemical modificationChemical toolsImagingProtein design
10.1038/S41589-021-00775-W
ISSN:1552-4450
Characterizing the regulatory Fas (CD95) epitope critical for agonist antibody targeting and CAR-T bystander function in ovarian cancer
Tanmoy Mondal•Himanshu Gaur•Brice E. N. Wamba•Abby Grace Michalak•Camryn Stout等 13 人
Cell Death & Differentiation
2023
•2023/10/14
•00 p.1-24
Receptor clustering is the most critical step to activate extrinsic apoptosis by death receptors belonging to the TNF superfamily. Although clinically unsuccessful, using agonist antibodies, the death receptors-5 remains extensively studied from a cancer therapeutics perspective. However, despite it...
Cancer microenvironmentPreclinical researchTumour heterogeneity
10.1038/S41418-023-01229-7
ISSN:1350-9047
SARS-CoV-2 immune repertoire in MIS-C and pediatric COVID-19
Ravichandran Supriya•Tang Juanjie•Grubbs Gabrielle•Lee Youri•Pourhashemi Sara等 13 人
Nature Immunology
2021
•2021/10/5
•00 p.1-13
There is limited understanding of the viral antibody fingerprint following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children. Herein, SARS-CoV-2 proteome-wide immunoprofiling of children with mild/moderate or severe coronavirus disease 2019 (COVID-19) versus multisys...
SARS-CoV-2Viral infection
10.1038/S41590-021-01051-8
ISSN:1529-2908
Small molecule targeting r(UGGAA) n disrupts RNA foci and alleviates disease phenotype in Drosophila model
Tomonori Shibata•Konami Nagano•Morio Ueyama•Kensuke Ninomiya•Tetsuro Hirose等 9 人
Nature Communications
2021
•2021/1/11
•Vol.12 No.1 p.1-13
Synthetic small molecules modulating RNA structure and function have therapeutic potential for RNA diseases. Here we report our discovery that naphthyridine carbamate dimer (NCD) targets disease-causing r(UGGAA)n repeat RNAs in spinocerebellar ataxia type 31 (SCA31). Structural analysis of the NCD-U...
Long non-coding RNAsNeurodegenerationNMR spectroscopyRNASmall molecules
10.1038/S41467-020-20487-4
ISSN:2041-1723
An Oryza-specific histone H4 variant predisposes H4 lysine 5 acetylation to modulate salt stress responses
Vivek Hari-Sundar Gandhivel•Paula Sotelo-Parrilla•Steffi Raju•Shaileshanand Jha•Anjitha Gireesh等 11 人
Nature Plants
2025
•2025/4/8
•00 p.1-18
Paralogous variants of canonical histones guide accessibility to DNA and function as additional layers of genome regulation. Across eukaryotes, the mechanism of action and functional significance of several variants of core histones are well known except those of histone H4. Here we show that a vari...
Cryoelectron microscopyEpigenomicsGene silencingPlant geneticsStress signalling
10.1038/S41477-025-01974-2
ISSN:2055-0278
Trefoil factors share a lectin activity that defines their role in mucus
Michael A. Järvå•James P. Lingford•Alan John•Niccolay Madiedo Soler•Nichollas E. Scott等 6 人
Nature Communications
2020
•2020/5/13
•Vol.11 No.1 p.1-9
The mucosal epithelium secretes a host of protective disulfide-rich peptides, including the trefoil factors (TFFs). The TFFs increase the viscoelasticity of the mucosa and promote cell migration, though the molecular mechanisms underlying these functions have remained poorly defined. Here, we demons...
GlycobiologyGlycoconjugatesLectinsPeptidesX-ray crystallography
10.1038/S41467-020-16223-7
ISSN:2041-1723
Molecular basis for human respiratory syncytial virus transcriptional regulator NS1 interactions with MED25
Parismita Kalita•Oam Khatavkar•Grace Uwase•Yulia Korshunova•Yuying Hu等 15 人
Nature Communications
2025
•2025/3/25
•Vol.16 No.1 p.1-14
The Mediator complex facilitates interactions between transcription factors and RNA polymerase II, a process that is required for host gene transcription, including in response to viral infections. Among the many subunits in the Mediator complex, the MED25 subunit has been shown to be a target for v...
Viral proteinsVirus–host interactionsX-ray crystallography
10.1038/S41467-025-58216-4
ISSN:2041-1723
Structural insights into the catalytic mechanism of ammonia monooxygenase
Xiaoyun Yang•Zongqiang Li•Tie-Qiang Mao•Chaofu Ma•Guo-Hao Chen等 7 人
Nature Communications
2025
•2025/12/12
0Ammonia monooxygenase (AMO) oxidizes ammonia to hydroxylamine. Limited knowledge of the structural information of AMO hinders our understanding of the molecular mechanism underlying ammonia oxidation, impacting the mitigation of greenhouse gas emissions and enhancing agricultural productivity using ...
Cryoelectron microscopyEnzyme mechanismsEnzymes
10.1038/S41467-025-67194-6
ISSN:2041-1723
Structures of distant diphtheria toxin homologs reveal functional determinants of an evolutionarily conserved toxin scaffold
Sugiman-Marangos Seiji N.•Gill Shivneet K.•Mansfield Michael J.•Orrell Kathleen E.•Doxey Andrew C.等 6 人
Communications Biology
2022
•2022/4/19
•Vol.5 No.1 p.1-12
Diphtheria toxin (DT) is the archetype for bacterial exotoxins implicated in human diseases and has played a central role in defining the field of toxinology since its discovery in 1888. Despite being one of the most extensively characterized bacterial toxins, the origins and evolutionary adaptation...
Molecular evolutionPathogensTransferasesX-ray crystallography
10.1038/S42003-022-03333-9
ISSN:2399-3642
Global analysis of biosynthetic gene clusters reveals conserved and unique natural products in entomopathogenic nematode-symbiotic bacteria
Shi Yi-Ming•Hirschmann Merle•Shi Yan-Ni•Ahmed Shabbir•Abebew Desalegne等 19 人
Nature Chemistry
2022
•2022/4/25
•00 p.1-12
Microorganisms contribute to the biology and physiology of eukaryotic hosts and affect other organisms through natural products. Xenorhabdus and Photorhabdus (XP) living in mutualistic symbiosis with entomopathogenic nematodes generate natural products to mediate bacteria–nematode–insect interaction...
Chemical ecologyMicrobial ecologyNatural productsSymbiosis
10.1038/S41557-022-00923-2
ISSN:1755-4330
Biocatalysis enables the scalable conversion of biobased furans into various furfurylamines
Pritam Giri•Seonga Lim•Taresh P. Khobragade•Amol D. Pagar•Mahesh D. Patil等 16 人
Nature Communications
2024
•2024/7/29
•Vol.15 No.1 p.1-10
Biobased furans have emerged as chemical building blocks for the development of materials because of their diverse scaffolds and as they can be directly prepared from sugars. However, selective, efficient, and cost-effective scalable conversion of biobased furans remains elusive. Here, we report a r...
BiocatalysisOxidoreductasesTransferasesX-ray crystallography
10.1038/S41467-024-50637-X
ISSN:2041-1723
Mechanistic insights into the structure and function of the RecA C-terminal tail
Lu Su•Xiaofan Li•Feifan Wang•Mengzhen Wang•Yimin Lu等 13 人
Communications Biology
2026
•2026/3/4
•Vol.9 No.1 p.5260
Bacterial RecA protein oligomerizes on single-stranded DNA (ssDNA) in the presence of ATP to form an active filament, RecA*, which is essential for homologous recombination and the activation of bacterial DNA damage response (SOS response). Despite extensive studies on the structure and function of ...
Double-strand DNA breaksNucleotide-binding proteinsX-ray crystallography
10.1038/S42003-026-09788-4
ISSN:2399-3642
Analysis of SARS-CoV-2 mutations in the United States suggests presence of four substrains and novel variants
Rui Wang•Jiahui Chen•Kaifu Gao•Yuta Hozumi•Changchuan Yin等 6 人
Communications Biology
2021
•2021/2/15
•Vol.4 No.1 p.1-14
SARS-CoV-2 has been mutating since it was first sequenced in early January 2020. Here, we analyze 45,494 complete SARS-CoV-2 geneome sequences in the world to understand their mutations. Among them, 12,754 sequences are from the United States. Our analysis suggests the presence of four substrains an...
Genome informaticsSARS-CoV-2Viral infection
10.1038/S42003-021-01754-6
ISSN:2399-3642
Enantioselective C(sp3)–C(sp3) bond formation by synergistic thiamine-dependent radical biocatalysis and photoredox catalysis
Jianlin Chun•Yuyan Bao•Qiaoyu Zhang•Xueli Hou•Zhouping Wu等 13 人
Nature Catalysis
2026
•2026/4/2
•00 p.1-10
Radical C(sp3)–C(sp3) bond formation has emerged as a promising strategy for constructing molecules rich in C(sp3)–stereocentres. However, achieving chemo- and enantioselective recombination of two prochiral alkyl radicals remains a substantial challenge. Here we synergistically repurpose a thiamine...
Asymmetric catalysisBiocatalysisEnzymesSynthetic chemistry methodology
10.1038/S41929-026-01515-W
ISSN:2520-1158
Reprogramming of bacterial virulence by lysine acetylation
Ole Schmöker•Britta Girbardt•Sabrina Schulze•Gottfried J. Palm•Leona Berndt等 29 人
Nature Communications
2026
•2026/4/27
•Vol.17 No.1 p.38590
Gram-negative bacteria use a plethora of virulence factors to infect eukaryotic cells. CE-clan protease-related virulence factors were reported to act as deubiquitinases/ubiquitin-like specific proteases. Some have an additional acetyl-transferase activity. The molecular mechanisms underlying this d...
Enzyme mechanismsNanocrystallography
10.1038/S41467-026-72244-8
ISSN:2041-1723
Global reference mapping of human transcription factor footprints
Jeff Vierstra•John Lazar•Richard Sandstrom•Jessica Halow•Kristen Lee等 19 人
Nature
2020
•2020/7/29
•Vol.583 No.7818 p.729-736
Combinatorial binding of transcription factors to regulatory DNA underpins gene regulation in all organisms. Genetic variation in regulatory regions has been connected with diseases and diverse phenotypic traits1, but it remains challenging to distinguish variants that affect regulatory function2. G...
EpigenomicsFunctional genomicsGene regulation
10.1038/S41586-020-2528-X
ISSN:0028-0836
A paired sequence language model for protein-protein interaction modeling
Jun Liu•Hungyu Chen•Yang Zhang
Nature Communications
2026
•2026/3/10
0Understanding protein–protein interactions (PPIs) is crucial for deciphering cellular processes and guiding therapeutic discovery. While recent protein language models have advanced sequence-based protein representation, most are designed for individual chains and fail to capture inherent PPI patter...
Computational modelsMachine learningProtein structure predictions
10.1038/S41467-026-70457-5
ISSN:2041-1723
Structural basis for the different states of the spike protein of SARS-CoV-2 in complex with ACE2
Renhong Yan•Yuanyuan Zhang•Yaning Li•Fangfei Ye•Yingying Guo等 9 人
Cell Research
2021
•2021/3/18
•00 p.1-3
Cryoelectron microscopyMechanisms of disease
10.1038/S41422-021-00490-0
ISSN:1001-0602
Identification of neutralizing nanobodies protecting against poxvirus infection
Xuehua Yang•Li Guo•Huarui Duan•Miao Fan•Fengwen Xu等 16 人
Cell Discovery
2025
•2025/3/25
•Vol.11 No.1 p.1-15
An outbreak of mpox has triggered concerns regarding the adequacy of intervention strategies. Passive immunity conferred by neutralizing antibodies exhibits potential in the prophylaxis and treatment of orthopoxvirus infections. Despite this, the investigations of effective antibody therapeutics hav...
Biological techniquesImmunology
10.1038/S41421-025-00771-7
ISSN:2056-5968
A strategic Ser/Cys exchange in the catalytic triad unlocks an acyltransferase-mediated synthesis of thioesters and tertiary amides
Martina L. Contente•David Roura Padrosa•Francesco Molinari•Francesca Paradisi
Nature Catalysis
2020
•2020/11/30
•Vol.3 No.12 p.1020-1026
Expanding the toolbox of enzymatic reactions accessible to organic chemists is one of the major goals in biocatalysis. Here we describe the development of an acyltransferase variant from Mycobacterium smegmatis in which a strategic Ser/Cys exchange in the catalytic triad dramatically expanded its sy...
BiocatalysisProtein designTransferases
10.1038/S41929-020-00539-0
ISSN:2520-1158
Efficient and accurate large library ligand docking with KarmaDock
Xujun Zhang•Odin Zhang•Chao Shen•Wanglin Qu•Shicheng Chen等 19 人
Nature Computational Science
2023
•2023/9/21
•Vol.3 No.9 p.789-804
Ligand docking is one of the core technologies in structure-based virtual screening for drug discovery. However, conventional docking tools and existing deep learning tools may suffer from limited performance in terms of speed, pose quality and binding affinity accuracy. Here we propose KarmaDock, a...
CheminformaticsVirtual screening
10.1038/S43588-023-00511-5
ISSN:2662-8457
HLA class I signal peptide polymorphism determines the level of CD94/NKG2–HLA-E-mediated regulation of effector cell responses
Zhansong Lin•Arman A. Bashirova•Mathias Viard•Lee Garner•Max Quastel等 19 人
Nature Immunology
2023
•2023/6/1
•00 p.1-11
Human leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and CD94/NKG2C receptors expressed on natural killer and T cell subsets. We show that among 16 common classical HLA class I SP variants, only 6 can be...
ImmunogeneticsImmunopathogenesis
10.1038/S41590-023-01523-Z
ISSN:1529-2908
Broader-species receptor binding and structural bases of Omicron SARS-CoV-2 to both mouse and palm-civet ACE2s
Li Linjie•Han Pu•Huang Baihan•Xie Yufeng•Li Weiwei等 20 人
Cell Discovery
2022
•2022/7/12
•Vol.8 No.1 p.1-16
The Omicron variant of SARS-CoV-2 carries multiple unusual mutations, particularly in the receptor-binding domain (RBD) of the spike (S) protein. Moreover, host-adapting mutations, such as residues 493, 498, and 501, were also observed in the Omicron RBD, which indicates that it is necessary to eval...
Electron microscopyX-ray crystallography
10.1038/S41421-022-00431-0
ISSN:2056-5968
Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses
Lu Xue•Tiancai Chang•Zimu Li•Chenchen Wang•Heyu Zhao等 16 人
Nature Communications
2024
•2024/5/30
•Vol.15 No.1 p.1-16
Influenza viruses and thogotoviruses account for most recognized orthomyxoviruses. Thogotoviruses, exemplified by Thogoto virus (THOV), are capable of infecting humans using ticks as vectors. THOV transcribes mRNA without the extraneous 5′ end sequences derived from cap-snatching in influenza virus ...
Cryoelectron microscopyEnzyme mechanismsInfluenza virusNucleic acidsVirus–host interactions
10.1038/S41467-024-48848-3
ISSN:2041-1723
Impaired 2′,3′-cyclic phosphate tRNA repair causes thermo-sensitive genic male sterility in rice
Bin Yan•Chunyan Liu•Jing Sun•Yang Mao•Can Zhou等 19 人
Cell Research
2024
•2024/9/9
•00 p.1-13
Hybrid rice, widely planted in Asia, is pathogen resistant and has superior yields, making it a major contributor to global food security. The two-line hybrid rice system, which utilizes mutants exhibiting photo-/thermo-sensitive genic male sterility (P/TGMS), is the leading hybrid rice breeding tec...
Biological techniquesPlant sciences
10.1038/S41422-024-01012-4
ISSN:1748-7838
Structural underpinnings of Ric8A function as a G-protein α-subunit chaperone and guanine-nucleotide exchange factor
Dhiraj Srivastava•Lokesh Gakhar•Nikolai O. Artemyev
Nature Communications
2019
•2019/7/12
•Vol.10 No.1 p.1-14
Resistance to inhibitors of cholinesterase 8A (Ric8A) is an essential regulator of G protein α-subunits (Gα), acting as a guanine nucleotide exchange factor and a chaperone. We report two crystal structures of Ric8A, one in the apo form and the other in complex with a tagged C-terminal fragment of G...
GTP-binding protein regulatorsMolecular modellingX-ray crystallography
10.1038/S41467-019-11088-X
ISSN:2041-1723
Analysis of diverse double-strand break synapsis with Polλ reveals basis for unique substrate specificity in nonhomologous end-joining
Kaminski Andrea M.•Chiruvella Kishore K.•Ramsden Dale A.•Bebenek Katarzyna•Kunkel Thomas A.等 6 人
Nature Communications
2022
•2022/7/1
•Vol.13 No.1 p.1-14
DNA double-strand breaks (DSBs) threaten genomic stability, since their persistence can lead to loss of critical genetic information, chromosomal translocations or rearrangements, and cell death. DSBs can be repaired through the nonhomologous end-joining pathway (NHEJ), which processes and ligates D...
DNAX-ray crystallography
10.1038/S41467-022-31278-4
ISSN:2041-1723
Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines
Linling He•Anshul Chaudhary•Xiaohe Lin•Cindy Sou•Tanwee Alkutkar等 13 人
Nature Communications
2021
•2021/5/11
•Vol.12 No.1 p.1-18
Ebola virus (EBOV) glycoprotein (GP) can be recognized by neutralizing antibodies (NAbs) and is the main target for vaccine design. Here, we first investigate the contribution of the stalk and heptad repeat 1-C (HR1C) regions to GP metastability. Specific stalk and HR1C modifications in a mucin-dele...
Humoral immunityProtein vaccinesX-ray crystallography
10.1038/S41467-021-22867-W
ISSN:2041-1723
Generation of a more efficient prime editor 2 by addition of the Rad51 DNA-binding domain
Song Myungjae•Lim Jung Min•Min Seonwoo•Oh Jeong-Seok•Kim Dong Young等 10 人
Nature Communications
2021
•2021/9/23
•Vol.12 No.1 p.1-8
Although prime editing is a promising genome editing method, the efficiency of prime editor 2 (PE2) is often insufficient. Here we generate a more efficient variant of PE2, named hyPE2, by adding the Rad51 DNA-binding domain. When tested at endogenous sites, hyPE2 shows a median of 1.5- or 1.4- fold...
CRISPR-Cas9 genome editingGenetic engineeringMolecular engineering
10.1038/S41467-021-25928-2
ISSN:2041-1723
Structures of the promoter-bound respiratory syncytial virus polymerase
Dongdong Cao•Yunrong Gao•Zhenhang Chen•Inesh Gooneratne•Claire Roesler等 15 人
Nature
2023
•2023/12/20
•Vol.625 No.7995 p.611-617
The respiratory syncytial virus (RSV) polymerase is a multifunctional RNA-dependent RNA polymerase composed of the large (L) protein and the phosphoprotein (P). It transcribes the RNA genome into ten viral mRNAs and replicates full-length viral genomic and antigenomic RNAs1. The RSV polymerase initi...
Cryoelectron microscopyVirus structures
10.1038/S41586-023-06867-Y
ISSN:0028-0836
Chemical capture of diazo metabolites reveals biosynthetic hydrazone oxidation
Katarina Pfeifer•Devon Van Cura•Kelvin J. Y. Wu•Emily P. Balskus
Nature
2026
•2026/2/4
•Vol.652 No.8109 p.517-525
Chemically reactive microbial natural products have enabled therapeutic development1 via their well-established anticancer, antibiotic and antioxidant activities. However, discovery of reactive metabolites is particularly challenging because they may not tolerate traditional bioactivity-guided isola...
Chemical toolsMetabolomicsOxidoreductases
10.1038/S41586-025-10079-X
ISSN:0028-0836
Structural insight into synergistic activation of human 3-methylcrotonyl-CoA carboxylase
Jiayue Su•Xuyang Tian•Hang Cheng•Desheng Liu•Ziyi Wang等 8 人
Nature Structural & Molecular Biology
2024
•2024/9/2
•00 p.1-13
The enzymes 3-methylcrotonyl-coenzyme A (CoA) carboxylase (MCC), pyruvate carboxylase and propionyl-CoA carboxylase belong to the biotin-dependent carboxylase family located in mitochondria. They participate in various metabolic pathways in human such as amino acid metabolism and tricarboxylic acid ...
Cryoelectron microscopyMetabolismMultienzyme complexes
10.1038/S41594-024-01379-3
ISSN:1545-9993
A substrate binding model for the KEOPS tRNA modifying complex
Jonah Beenstock•Samara Mishelle Ona•Jennifer Porat•Stephen Orlicky•Leo C. K. Wan等 17 人
Nature Communications
2020
•2020/12/4
•Vol.11 No.1 p.1-17
The KEOPS complex, which is conserved across archaea and eukaryotes, is composed of four core subunits; Pcc1, Kae1, Bud32 and Cgi121. KEOPS is crucial for the fitness of all organisms examined. In humans, pathogenic mutations in KEOPS genes lead to Galloway–Mowat syndrome, an autosomal-recessive dis...
Chemical modificationRNA modificationtRNAsX-ray crystallography
10.1038/S41467-020-19990-5
ISSN:2041-1723
Discovery and structural characterization of monkeypox virus methyltransferase VP39 inhibitors reveal similarities to SARS-CoV-2 nsp14 methyltransferase
Silhan Jan•Klima Martin•Otava Tomas•Skvara Petr•Chalupska Dominika等 9 人
Nature Communications
2023
•2023/4/20
•Vol.14 No.1 p.1-9
Monkeypox is a disease with pandemic potential. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus from the Poxviridae family, that replicates in the cytoplasm and must encode for its own RNA processing machinery including the capping machinery. Here, we present crystal structur...
AntiviralsPox virusTransferasesX-ray crystallography
10.1038/S41467-023-38019-1
ISSN:2041-1723
Human PRPS1 filaments stabilize allosteric sites to regulate activity
Hvorecny Kelli L.•Hargett Kenzee•Quispe Joel D.•Kollman Justin M.
Nature Structural & Molecular Biology
2023
•2023/2/6
•Vol.30 No.3 p.391-402
The universally conserved enzyme phosphoribosyl pyrophosphate synthetase (PRPS) assembles filaments in evolutionarily diverse organisms. PRPS is a key regulator of nucleotide metabolism, and mutations in the human enzyme PRPS1 lead to a spectrum of diseases. Here we determine structures of human PRP...
Cryoelectron microscopyEnzyme mechanismsNucleotide-binding proteinsSupramolecular assemblyTransferases
10.1038/S41594-023-00921-Z
ISSN:1545-9993
Electron-density-informed effective and reliable de novo molecular design and optimization with ED2Mol
Mingyu Li•Kun Song•Jixiao He•Mingzhu Zhao•Gengshu You等 24 人
Nature Machine Intelligence
2025
•2025/8/20
•Vol.7 No.8 p.1355-1368
Generative drug design opens avenues for discovering novel compounds within the vast chemical space rather than conventional screening against limited libraries. However, the practical utility of the generated molecules is frequently constrained, as many designs prioritize a narrow range of pharmaco...
Drug discoveryMachine learning
10.1038/S42256-025-01095-7
ISSN:2522-5839
Structure of the human plasma membrane Ca 2+ -ATPase 1 in complex with its obligatory subunit neuroplastin
Deshun Gong•Ximin Chi•Kang Ren•Gaoxingyu Huang•Gewei Zhou等 8 人
Nature Communications
2018
•2018/9/6
•Vol.9 No.1 p.1-9
Plasma membrane Ca2+-ATPases (PMCAs) are key regulators of global Ca2+ homeostasis and local intracellular Ca2+ dynamics. Recently, Neuroplastin (NPTN) and basigin were identified as previously unrecognized obligatory subunits of PMCAs that dramatically increase the efficiency of PMCA-mediated Ca2+ ...
Cryoelectron microscopyMembrane proteins
10.1038/S41467-018-06075-7
ISSN:2041-1723
Methionine in a protein hydrophobic core drives tight interactions required for assembly of spider silk
Julia C. Heiby•Benedikt Goretzki•Christopher M. Johnson•Ute A. Hellmich•Hannes Neuweiler
Nature Communications
2019
•2019/9/26
•Vol.10 No.1 p.1-14
Web spiders connect silk proteins, so-called spidroins, into fibers of extraordinary toughness. The spidroin N-terminal domain (NTD) plays a pivotal role in this process: it polymerizes spidroins through a complex mechanism of dimerization. Here we analyze sequences of spidroin NTDs and find an unus...
Circular dichroismFluorescence spectroscopyProtein foldingSolution-state NMR
10.1038/S41467-019-12365-5
ISSN:2041-1723
A variational expectation-maximization framework for balanced multi-scale learning of protein and drug interactions
Jiahua Rao•Jiancong Xie•Qianmu Yuan•Deqin Liu•Zhen Wang等 8 人
Nature Communications
2024
•2024/5/25
•Vol.15 No.1 p.1-12
Protein functions are characterized by interactions with proteins, drugs, and other biomolecules. Understanding these interactions is essential for deciphering the molecular mechanisms underlying biological processes and developing new therapeutic strategies. Current computational methods mostly pre...
Data integrationProteome informaticsVirtual drug screening
10.1038/S41467-024-48801-4
ISSN:2041-1723
Binding and structural basis of equine ACE2 to RBDs from SARS-CoV, SARS-CoV-2 and related coronaviruses
Xu Zepeng•Kang Xinrui•Han Pu•Du Pei•Li Linjie等 12 人
Nature Communications
2022
•2022/6/21
•Vol.13 No.1 p.1-11
The origin and host range of SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), are important scientific questions as they might provide insight into understanding of the potential future spillover to infect humans. Here, we tested the binding between equine angiotensin converti...
NanocrystallographyPathogensSARS-CoV-2
10.1038/S41467-022-31276-6
ISSN:2041-1723
Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors
Jerzy Osipiuk•Saara-Anne Azizi•Steve Dvorkin•Michael Endres•Robert Jedrzejczak等 21 人
Nature Communications
2021
•2021/2/2
•Vol.12 No.1 p.1-9
The pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to expand. Papain-like protease (PLpro) is one of two SARS-CoV-2 proteases potentially targetable with antivirals. PLpro is an attractive target because it plays an essential role in cleavage and maturation...
Molecular biologyProteasesX-ray crystallography
10.1038/S41467-021-21060-3
ISSN:2041-1723
Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations
Isao Miyazaki•Igor Odintsov•Keiji Ishida•Allan J. W. Lui•Masanori Kato等 33 人
Nature Cancer
2023
•2023/9/21
•Vol.4 No.9 p.1345-1361
RET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The...
CancerKinasesMechanisms of diseaseStructure-based drug designTargeted therapies
10.1038/S43018-023-00630-Y
ISSN:2662-1347
Protein shape sampled by ion mobility mass spectrometry consistently improves protein structure prediction
Turzo SM Bargeen Alam•Seffernick Justin T.•Rolland Amber D.•Donor Micah T.•Heinze Sten等 8 人
Nature Communications
2022
•2022/7/28
•Vol.13 No.1 p.1-15
Ion mobility (IM) mass spectrometry provides structural information about protein shape and size in the form of an orientationally-averaged collision cross-section (CCSIM). While IM data have been used with various computational methods, they have not yet been utilized to predict monomeric protein s...
Computational biophysicsMass spectrometryMolecular modellingProtein structure predictions
10.1038/S41467-022-32075-9
ISSN:2041-1723
Peri active site catalysis of proline isomerisation is the molecular basis of allomorphy in β-phosphoglucomutase
F. Aaron Cruz-Navarrete•Nicola J. Baxter•Adam J. Flinders•Anamaria Buzoianu•Matthew J. Cliff等 7 人
Communications Biology
2024
•2024/7/27
•Vol.7 No.1 p.1-14
Metabolic regulation occurs through precise control of enzyme activity. Allomorphy is a post-translational fine control mechanism where the catalytic rate is governed by a conformational switch that shifts the enzyme population between forms with different activities. β-Phosphoglucomutase (βPGM) use...
BiocatalysisBiophysical chemistryEnzyme mechanismsSolution-state NMRX-ray crystallography
10.1038/S42003-024-06577-9
ISSN:2399-3642
Flavin-dependent halogenases catalyze enantioselective olefin halocyclization
Dibyendu Mondal•Brian F. Fisher•Yuhua Jiang•Jared C. Lewis
Nature Communications
2021
•2021/6/1
•Vol.12 No.1 p.1-7
Halocyclization of alkenes is a powerful bond-forming tool in synthetic organic chemistry and a key step in natural product biosynthesis, but catalyzing halocyclization with high enantioselectivity remains a challenging task. Identifying suitable enzymes that catalyze enantioselective halocyclizatio...
BiocatalysisNatural product synthesisOxidoreductases
10.1038/S41467-021-23503-3
ISSN:2041-1723
Structure-guided design of a synthetic bile acid that inhibits Clostridioides difficile TcdB toxin
Sean Miletic•Simoun Icho•Zhijie Li•John Tam•Elizabeth C. Rose等 13 人
Nature Microbiology
2025
•2025/11/18
•00 p.1-14
Intestinal bile acids are a family of host and microbiota metabolites that can directly inhibit toxin B (TcdB), the primary virulence factor of Clostridioides difficile that causes infectious diarrhoea and colitis. However, the mechanism underlying the inhibition is unclear. Here we used cryogenic e...
Drug discovery and developmentPathogens
10.1038/S41564-025-02179-1
ISSN:2058-5276
Mechanistic insights into the evolution of DUF26-containing proteins in land plants
Aleksia Vaattovaara•Benjamin Brandt•Sitaram Rajaraman•Omid Safronov•Andres Veidenberg等 11 人
Communications Biology
2019
•2019/2/8
•Vol.2 No.1 p.1-18
Large protein families are a prominent feature of plant genomes and their size variation is a key element for adaptation. However, gene and genome duplications pose difficulties for functional characterization and translational research. Here we infer the evolutionary history of the DOMAIN OF UNKNOW...
Molecular evolutionPlant evolutionPlant signallingX-ray crystallography
10.1038/S42003-019-0306-9
ISSN:2399-3642
Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex
Antonín Brisuda•James C. S. Ho•Pancham S. Kandiyal•Justin T-Y. Ng•Ines Ambite等 21 人
Nature Communications
2021
•2021/6/8
•Vol.12 No.1 p.1-16
Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical pep...
Cancer therapyDrug discoveryStructural biology
10.1038/S41467-021-23748-Y
ISSN:2041-1723
Non-modular fatty acid synthases yield distinct N-terminal acylation in ribosomal peptides
Hengqian Ren•Chunshuai Huang•Yuwei Pan•Shravan R. Dommaraju•Haiyang Cui等 9 人
Nature Chemistry
2024
•2024/3/25
•00 p.1-10
Recent efforts in genome mining of ribosomally synthesized and post-translationally modified peptides (RiPPs) have expanded the diversity of post-translational modification chemistries. However, RiPPs are rarely reported as hybrid molecules incorporating biosynthetic machinery from other natural pro...
BiosynthesisEnzyme mechanismsMultienzyme complexes
10.1038/S41557-024-01491-3
ISSN:1755-4330
TAPBPR promotes antigen loading on MHC-I molecules using a peptide trap
Andrew C. McShan•Christine A. Devlin•Giora I. Morozov•Sarah A. Overall•Danai Moschidi等 8 人
Nature Communications
2021
•2021/5/26
•Vol.12 No.1 p.1-18
Chaperones Tapasin and TAP-binding protein related (TAPBPR) perform the important functions of stabilizing nascent MHC-I molecules (chaperoning) and selecting high-affinity peptides in the MHC-I groove (editing). While X-ray and cryo-EM snapshots of MHC-I in complex with TAPBPR and Tapasin, respecti...
BiochemistryMHC class INMR spectroscopy
10.1038/S41467-021-23225-6
ISSN:2041-1723
Sm-like protein Rof inhibits transcription termination factor ρ by binding site obstruction and conformational insulation
Nelly Said•Mark Finazzo•Tarek Hilal•Bing Wang•Tim Luca Selinger等 8 人
Nature Communications
2024
•2024/4/15
•Vol.15 No.1 p.1-18
Transcription termination factor ρ is a hexameric, RNA-dependent NTPase that can adopt active closed-ring and inactive open-ring conformations. The Sm-like protein Rof, a homolog of the RNA chaperone Hfq, inhibits ρ-dependent termination in vivo but recapitulation of this activity in vitro has prove...
Bacterial structural biologyCryoelectron microscopyTranscriptionTranscription factors
10.1038/S41467-024-47439-6
ISSN:2041-1723
SepF is the FtsZ anchor in archaea, with features of an ancestral cell division system
Nika Pende•Adrià Sogues•Daniela Megrian•Anna Sartori-Rupp•Patrick England等 11 人
Nature Communications
2021
•2021/6/4
•Vol.12 No.1 p.1-13
Most archaea divide by binary fission using an FtsZ-based system similar to that of bacteria, but they lack many of the divisome components described in model bacterial organisms. Notably, among the multiple factors that tether FtsZ to the membrane during bacterial cell constriction, archaea only po...
Archaeal biologyCell divisionCellular microbiology
10.1038/S41467-021-23099-8
ISSN:2041-1723
Structural basis of substrate recognition by human tRNA splicing endonuclease TSEN
Samoil Sekulovski•Lukas Sušac•Lukas S. Stelzl•Robert Tampé•Simon Trowitzsch
Nature Structural & Molecular Biology
2023
•2023/5/25
•00 p.1-7
Heterotetrameric human transfer RNA (tRNA) splicing endonuclease TSEN catalyzes intron excision from precursor tRNAs (pre-tRNAs), utilizing two composite active sites. Mutations in TSEN and its associated RNA kinase CLP1 are linked to the neurodegenerative disease pontocerebellar hypoplasia (PCH). D...
Cryoelectron microscopyEnzyme mechanismsRNASmall RNAstRNAs
10.1038/S41594-023-00992-Y
ISSN:1545-9993
Structural basis of substrate recognition and allosteric activation of the proapoptotic mitochondrial HtrA2 protease
Emelie E. Aspholm•Jens Lidman•Björn M. Burmann
Nature Communications
2024
•2024/5/30
•Vol.15 No.1 p.1-18
The mitochondrial serine protease HtrA2 is a human homolog of the Escherichia coli Deg-proteins exhibiting chaperone and proteolytic roles. HtrA2 is involved in both apoptotic regulation via its ability to degrade inhibitor-of-apoptosis proteins (IAPs), as well as in cellular maintenance as part of ...
Mitochondrial proteinsProteasesSolution-state NMR
10.1038/S41467-024-48997-5
ISSN:2041-1723
A small-molecule PI3Kα activator for cardioprotection and neuroregeneration
Grace Q. Gong•Benoit Bilanges•Ben Allsop•Glenn R. Masson•Victoria Roberton等 41 人
Nature
2023
•2023/5/24
•00 p.1-10
Harnessing the potential beneficial effects of kinase signalling through the generation of direct kinase activators remains an underexplored area of drug development1–5. This also applies to the PI3K signalling pathway, which has been extensively targeted by inhibitors for conditions with PI3K overa...
Cell signallingDrug discoveryKinasesX-ray crystallography
10.1038/S41586-023-05972-2
ISSN:0028-0836
Distribution and diversity of classical deacylases in bacteria
Leonie G. Graf•Carlos Moreno-Yruela•Chuan Qin•Sabrina Schulze•Gottfried J. Palm等 21 人
Nature Communications
2024
•2024/11/3
•Vol.15 No.1 p.1-31
Classical Zn2+-dependent deac(et)ylases play fundamental regulatory roles in life and are well characterized in eukaryotes regarding their structures, substrates and physiological roles. In bacteria, however, classical deacylases are less well understood. We construct a Generalized Profile (GP) and ...
Bacterial structural biologyHydrolasesX-ray crystallography
10.1038/S41467-024-53903-0
ISSN:2041-1723
MOC1 cleaves Holliday junctions through a cooperative nick and counter-nick mechanism mediated by metal ions
Danping Zhang•Shenjie Xu•Zhipu Luo•Zhonghui Lin
Nature Communications
2024
•2024/6/17
•Vol.15 No.1 p.1-9
Holliday junction resolution is a crucial process in homologous recombination and DNA double-strand break repair. Complete Holliday junction resolution requires two stepwise incisions across the center of the junction, but the precise mechanism of metal ion-catalyzed Holliday junction cleavage remai...
DNA damage and repairEnzyme mechanismsX-ray crystallography
10.1038/S41467-024-49490-9
ISSN:2041-1723
Inhibition of chitin deacetylases to attenuate plant fungal diseases
Lin Liu•Yeqiang Xia•Yingchen Li•Yong Zhou•Xiaofeng Su等 11 人
Nature Communications
2023
•2023/6/29
•Vol.14 No.1 p.1-12
Phytopathogenic fungi secrete chitin deacetylase (CDA) to escape the host’s immunological defense during infection. Here, we showed that the deacetylation activity of CDA toward chitin is essential for fungal virulence. Five crystal structures of two representative and phylogenetically distant phyto...
Effectors in plant pathologyVirulence
10.1038/S41467-023-39562-7
ISSN:2041-1723
Platelet integrin αIIbβ3 plays a key role in a venous thrombogenesis mouse model
Brian D. Adair•Conroy O. Field•José L. Alonso•Jian-Ping Xiong•Shi-Xian Deng等 15 人
Nature Communications
2024
•2024/10/4
•Vol.15 No.1 p.1-14
Venous thrombosis (VT) is a common vascular disease associated with reduced survival and a high recurrence rate. VT is initiated by the accumulation of platelets and neutrophils at sites of endothelial cell activation. A role for platelet αIIbβ3 in VT is not established, a task complicated by the in...
Cryoelectron microscopyMolecular medicine
10.1038/S41467-024-52869-3
ISSN:2041-1723
Structure of the human sodium leak channel NALCN in complex with FAM155A
Jiongfang Xie•Meng Ke•Lizhen Xu•Shiyi Lin•Jin Huang等 9 人
Nature Communications
2020
•2020/11/17
•Vol.11 No.1 p.1-13
NALCN, a sodium leak channel expressed mainly in the central nervous system, is responsible for the resting Na+ permeability that controls neuronal excitability. Dysfunctions of the NALCN channelosome, NALCN with several auxiliary subunits, are associated with a variety of human diseases. Here, we r...
Cryoelectron microscopyIon channels in the nervous system
10.1038/S41467-020-19667-Z
ISSN:2041-1723
Structural basis of the RNA-mediated Retron-Eco2 oligomerization
Yanjing Wang•Chen Wang•Yongqi Yin•Yongqing Cui•Zhikang Dai等 9 人
Cell Discovery
2025
•2025/9/2
•Vol.11 No.1 p.1-12
In the evolutionary arms race between bacteria and viruses, retrons have emerged as distinctive antiphage defense systems. Here, we elucidate the structure and function of Retron-Eco2, which comprises a non-coding RNA (ncRNA) that encodes multicopy single-stranded DNA (msDNA, a DNA‒RNA hybrid) and a...
Cryoelectron microscopyLong non-coding RNAs
10.1038/S41421-025-00823-Y
ISSN:2056-5968
Mapping and identification of soft corona proteins at nanoparticles and their impact on cellular association
Hossein Mohammad-Beigi•Yuya Hayashi•Christina Moeslund Zeuthen•Hoda Eskandari•Carsten Scavenius等 9 人
Nature Communications
2020
•2020/9/10
•Vol.11 No.1 p.1-16
The current understanding of the biological identity that nanoparticles may acquire in a given biological milieu is mostly inferred from the hard component of the protein corona (HC). The composition of soft corona (SC) proteins and their biological relevance have remained elusive due to the lack of...
Cell–particle interactionsNanobiotechnologyNanoscale biophysics
10.1038/S41467-020-18237-7
ISSN:2041-1723
Interpretable bilinear attention network with domain adaptation improves drug–target prediction
Bai Peizhen•Miljković Filip•John Bino•Lu Haiping
Nature Machine Intelligence
2023
•2023/2/2
•Vol.5 No.2 p.126-136
Predicting drug–target interaction is key for drug discovery. Recent deep learning-based methods show promising performance, but two challenges remain: how to explicitly model and learn local interactions between drugs and targets for better prediction and interpretation and how to optimize generali...
Computer scienceVirtual screening
10.1038/S42256-022-00605-1
ISSN:2522-5839
Comprehensive structural analysis reveals broad-spectrum neutralizing antibodies against SARS-CoV-2 Omicron variants
Chi Xiangyang•Xia Lingyun•Zhang Guanying•Chi Ximin•Huang Bangdong等 15 人
Cell Discovery
2023
•2023/4/4
•Vol.9 No.1 p.1-23
The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread around the world. Mutant strains of SARS-CoV-2 are constantly emerging. At present, Omicron variants have become mainstream. In this work, we carried out a systematic and comprehensive analysis of the reported spike protein antibodies...
ImmunologyStructural biology
10.1038/S41421-023-00535-1
ISSN:2056-5968
Accurate prediction of protein function using statistics-informed graph networks
Yaan J. Jang•Qi-Qi Qin•Si-Yu Huang•Arun T. John Peter•Xue-Ming Ding等 6 人
Nature Communications
2024
•2024/8/4
•Vol.15 No.1 p.1-12
Understanding protein function is pivotal in comprehending the intricate mechanisms that underlie many crucial biological activities, with far-reaching implications in the fields of medicine, biotechnology, and drug development. However, more than 200 million proteins remain uncharacterized, and com...
BioinformaticsComputational modelsMachine learningProtein function predictionsProtein sequencing
10.1038/S41467-024-50955-0
ISSN:2041-1723
Structural and biochemical insight into a modular β-1,4-galactan synthase in plants
Prabhakar Pradeep Kumar•Pereira Jose Henrique•Taujale Rahil•Shao Wanchen•Bharadwaj Vivek S.等 14 人
Nature Plants
2023
•2023/2/27
•Vol.9 No.3 p.486-500
Rhamnogalacturonan I (RGI) is a structurally complex pectic polysaccharide with a backbone of alternating rhamnose and galacturonic acid residues substituted with arabinan and galactan side chains. Galactan synthase 1 (GalS1) transfers galactose and arabinose to either extend or cap the β-1,4-galact...
Biochemical assaysBiofuelsBioinformaticsBiophysical methods
10.1038/S41477-023-01358-4
ISSN:2055-0278
Cosmopolitan marine bacteria facilitate a vast phytoplankton-derived sulfonate-based carbon flow through sulfoquinovosidases
Xiaoyi Ma•Huanyu Wang•Changjie Dong•Le Liu•Xuanyun Qiu等 12 人
Nature Communications
2025
•2025/12/5
0Sulfoquinovose (SQ) and sulfoquinovosyl glycerol (SQGro) are derived from abundant membrane sulfolipids termed sulfoquinovosyl diacylglycerols (SQDG) and produced by photosynthetic organisms, serving as sources of carbon and sulfur for bacteria. The conversion processes of these sulfoquinovosyl comp...
Microbial biooceanographyMicrobial ecology
10.1038/S41467-025-66898-Z
ISSN:2041-1723
Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products
Nathaniel C. Gilbert•Jana Gerstmeier•Erin E. Schexnaydre•Friedemann Börner•Ulrike Garscha等 8 人
Nature Chemical Biology
2020
•2020/5/11
•Vol.16 No.7 p.783-790
Leukotrienes (LT) are lipid mediators of the inflammatory response that are linked to asthma and atherosclerosis. LT biosynthesis is initiated by 5-lipoxygenase (5-LOX) with the assistance of the substrate-binding 5-LOX-activating protein at the nuclear membrane. Here, we contrast the structural and...
BiochemistryEnzymesLipidsStructural biology
10.1038/S41589-020-0544-7
ISSN:1552-4450
Mask-prior-guided denoising diffusion improves inverse protein folding
Peizhen Bai•Filip Miljković•Xianyuan Liu•Leonardo De Maria•Rebecca Croasdale-Wood等 7 人
Nature Machine Intelligence
2025
•2025/6/16
•00 p.1-13
Inverse protein folding generates valid amino acid sequences that can fold into a desired protein structure, with recent deep learning advances showing strong potential and competitive performance. However, challenges remain, such as predicting elements with high structural uncertainty, including di...
Computer scienceMachine learningProtein design
10.1038/S42256-025-01042-6
ISSN:2522-5839
Kinase interaction analysis predicts actions of the WNK-OSR1/SPAK pathway
Clinton A. Taylor•Ji-Ung Jung•Sachith Gallolu Kankanamalage•Justin Li•Magdalena Grzemska等 11 人
Communications Biology
2025
•2025/9/5
•Vol.8 No.1 p.1-18
The WNK-OSR1/SPAK protein kinase pathway regulates ion homeostasis and cell volume, but its other functions are not well understood. To discover undefined signaling functions, we utilized experimentally-derived binding specificity to predict interactions and relative affinities with the conserved C-...
BioinformaticsCellular signalling networksKinasesPeptidesProtein–protein interaction networks
10.1038/S42003-025-08551-5
ISSN:2399-3642
Nuclear export of pre-60S particles through the nuclear pore complex
Zongqiang Li•Shuaijiabin Chen•Liang Zhao•Guoqiang Huang•Huiqin Xu等 9 人
Nature
2023
•2023/5/31
•00 p.1-8
The nuclear pore complex (NPC) is the bidirectional gate that mediates the exchange of macromolecules or their assemblies between nucleus and cytoplasm1–3. The assembly intermediates of the ribosomal subunits, pre-60S and pre-40S particles, are among the largest cargoes of the NPC and the export of ...
Cryoelectron microscopyNuclear pore complexRibosome
10.1038/S41586-023-06128-Y
ISSN:0028-0836
Cryo-EM structures of full-length integrin αIIbβ3 in native lipids
Brian D. Adair•Jian-Ping Xiong•Mark Yeager•M. Amin Arnaout
Nature Communications
2023
•2023/7/13
•Vol.14 No.1 p.1-7
Platelet integrin αIIbβ3 is maintained in a bent inactive state (low affinity to physiologic ligand), but can rapidly switch to a ligand-competent (high-affinity) state in response to intracellular signals (“inside-out” activation). Once bound, ligands drive proadhesive “outside-in” signaling. Anti-...
Cryoelectron microscopyIntegrinsMechanism of actionMembrane proteins
10.1038/S41467-023-39763-0
ISSN:2041-1723
Dynamics of an LPS translocon induced by substrate and an antimicrobial peptide
Francesco Fiorentino•Joshua B. Sauer•Xingyu Qiu•Robin A. Corey•C. Keith Cassidy等 10 人
Nature Chemical Biology
2020
•2020/11/16
•Vol.17 No.2 p.187-195
Lipopolysaccharide (LPS) transport to the outer membrane (OM) is a crucial step in the biogenesis of microbial surface defenses. Although many features of the translocation mechanism have been elucidated, molecular details of LPS insertion via the LPS transport (Lpt) OM protein LptDE remain elusive....
Biophysical chemistryMicrobiologyProteinsStructural biologyTransporters
10.1038/S41589-020-00694-2
ISSN:1552-4450
Acetyl-CoA synthetase activity is enzymatically regulated by lysine acetylation using acetyl-CoA or acetyl-phosphate as donor molecule
Chuan Qin•Leonie G. Graf•Kilian Striska•Markus Janetzky•Norman Geist等 16 人
Nature Communications
2024
•2024/7/17
•Vol.15 No.1 p.1-22
The AMP-forming acetyl-CoA synthetase is regulated by lysine acetylation both in bacteria and eukaryotes. However, the underlying mechanism is poorly understood. The Bacillus subtilis acetyltransferase AcuA and the AMP-forming acetyl-CoA synthetase AcsA form an AcuA•AcsA complex, dissociating upon l...
Enzyme mechanismsEnzymesX-ray crystallography
10.1038/S41467-024-49952-0
ISSN:2041-1723
Structure of the reduced microsporidian proteasome bound by PI31-like peptides in dormant spores
Jespersen Nathan•Ehrenbolger Kai•Winiger Rahel R.•Svedberg Dennis•Vossbrinck Charles R.等 6 人
Nature Communications
2022
•2022/11/15
•Vol.13 No.1 p.1-14
Proteasomes play an essential role in the life cycle of intracellular pathogens with extracellular stages by ensuring proteostasis in environments with limited resources. In microsporidia, divergent parasites with extraordinarily streamlined genomes, the proteasome complexity and structure are unkno...
Cryoelectron microscopyMolecular evolutionPathogensProteasome
10.1038/S41467-022-34691-X
ISSN:2041-1723
Structural insights into the inhibition of glycine reuptake
Azadeh Shahsavar•Peter Stohler•Gleb Bourenkov•Iwan Zimmermann•Martin Siegrist等 12 人
Nature
2021
•2021/3/3
•Vol.591 No.7851 p.677-681
The human glycine transporter 1 (GlyT1) regulates glycine-mediated neuronal excitation and inhibition through the sodium- and chloride-dependent reuptake of glycine1–3. Inhibition of GlyT1 prolongs neurotransmitter signalling, and has long been a key strategy in the development of therapies for a br...
Enzyme mechanismsNanocrystallographyTransporters in the nervous system
10.1038/S41586-021-03274-Z
ISSN:0028-0836
Substrate specificity of a branch of aromatic dioxygenases determined by three distinct motifs
Chengsen Cui•Lu-Jia Yang•Zi-Wei Liu•Xian Shu•Wei-Wei Zhang等 11 人
Nature Communications
2024
•2024/9/3
•Vol.15 No.1 p.1-10
The inversion of substrate size specificity is an evolutionary roadblock for proteins. The Duf4243 dioxygenases GedK and BTG13 are known to catalyze the aromatic cleavage of bulky tricyclic hydroquinone. In this study, we discover a Duf4243 dioxygenase PaD that favors small monocyclic hydroquinones ...
BiocatalysisMolecular modellingOxidoreductases
10.1038/S41467-024-52101-2
ISSN:2041-1723
Structural insights into influenza A virus ribonucleoproteins reveal a processive helical track as transcription mechanism
Rocío Coloma•Rocío Arranz•José M. de la Rosa-Trevín•Carlos O. S. Sorzano•Sandie Munier等 9 人
Nature Microbiology
2020
•2020/3/9
•Vol.5 No.5 p.727-734
The influenza virus genome consists of eight viral ribonucleoproteins (vRNPs), each consisting of a copy of the polymerase, one of the genomic RNA segments and multiple copies of the nucleoprotein arranged in a double helical conformation. vRNPs are macromolecular machines responsible for messenger ...
Cryoelectron microscopyInfluenza virusTranscriptionVirology
10.1038/S41564-020-0675-3
ISSN:2058-5276
Histone H2A variants alpha1-extension helix directs RNF168-mediated ubiquitination
Jessica L. Kelliher•Kirk L. West•Qingguo Gong•Justin W. C. Leung
Nature Communications
2020
•2020/5/18
•Vol.11 No.1 p.1-14
Histone ubiquitination plays an important role in the DNA damage response (DDR) pathway. RNF168 catalyzes H2A and H2AX ubiquitination on lysine 13/15 (K13/K15) upon DNA damage and promotes the accrual of downstream repair factors at damaged chromatin. Here, we report that RNF168 ubiquitinates the no...
DNA damage responseHistone post-translational modificationsHistone variantsNucleosomes
10.1038/S41467-020-16307-4
ISSN:2041-1723
Characterization of a fold in TANGO1 evolved from SH3 domains for the export of bulky cargos
Arnolds Oliver•Stoll Raphael
Nature Communications
2023
•2023/4/20
•Vol.14 No.1 p.1-12
Bulky cargos like procollagens, apolipoproteins, and mucins exceed the size of conventional COPII vesicles. During evolution a process emerged in metazoans, predominantly governed by the TANGO1 protein family, that organizes cargo at the exit sites of the endoplasmic reticulum and facilitates export...
Molecular evolutionProtein transportSolution-state NMR
10.1038/S41467-023-37705-4
ISSN:2041-1723
Unconventional isoquinoline-based SERMs elicit fulvestrant-like transcriptional programs in ER+ breast cancer cells
Hancock G. R.•Young K. S.•Hosfield D. J.•Joiner C.•Sullivan E. A.等 9 人
Npj Breast Cancer
2022
•2022/12/14
•Vol.8 No.1 p.1-26
Estrogen receptor alpha (ERα) is a ligand-dependent master transcriptional regulator and key driver of breast cancer pathology. Small molecule hormones and competitive antagonists favor unique ERα conformational ensembles that elicit ligand-specific transcriptional programs in breast cancer and othe...
Breast cancerDrug developmentDrug discovery and development
10.1038/S41523-022-00497-9
ISSN:2374-4677
Multistate and functional protein design using RoseTTAFold sequence space diffusion
Sidney Lyayuga Lisanza•Jacob Merle Gershon•Samuel W. K. Tipps•Jeremiah Nelson Sims•Lucas Arnoldt等 19 人
Nature Biotechnology
2024
•2024/9/25
•00 p.1-11
Protein denoising diffusion probabilistic models are used for the de novo generation of protein backbones but are limited in their ability to guide generation of proteins with sequence-specific attributes and functional properties. To overcome this limitation, we developed ProteinGenerator (PG), a s...
Computational modelsMolecular engineeringProteins
10.1038/S41587-024-02395-W
ISSN:1087-0156
RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS
Avinash V. Dharmadhikari•Maria Alba Abad•Sheraz Khan•Reza Maroofian•Tristan T. Sands等 82 人
Nature Communications
2025
•2025/2/17
•Vol.16 No.1 p.1-24
SPOUT1/CENP-32 encodes a putative SPOUT RNA methyltransferase previously identified as a mitotic chromosome associated protein. SPOUT1/CENP-32 depletion leads to centrosome detachment from the spindle poles and chromosome misalignment. Aided by gene matching platforms, here we identify 28 individual...
Mechanisms of diseaseMitotic spindleNeurodevelopmental disorders
10.1038/S41467-025-56876-W
ISSN:2041-1723
Rep15 interacts with several Rab GTPases and has a distinct fold for a Rab effector
Rai Amrita•Singh Anurag K.•Bleimling Nathalie•Posern Guido•Vetter Ingrid R.等 6 人
Nature Communications
2022
•2022/7/23
•Vol.13 No.1 p.1-17
In their GTP-bound (active) form, Rab proteins interact with effector proteins that control downstream signaling. One such Rab15 effector is Rep15, which is known to have a role in receptor recycling from the endocytic recycling compartment but otherwise remains poorly characterized. Here, we report...
Intracellular signalling peptides and proteinsSmall GTPasesX-ray crystallography
10.1038/S41467-022-31831-1
ISSN:2041-1723
SQM2.20: Semiempirical quantum-mechanical scoring function yields DFT-quality protein–ligand binding affinity predictions in minutes
Adam Pecina•Jindřich Fanfrlík•Martin Lepšík•Jan Řezáč
Nature Communications
2024
•2024/2/6
•Vol.15 No.1 p.1-10
Accurate estimation of protein–ligand binding affinity is the cornerstone of computer-aided drug design. We present a universal physics-based scoring function, named SQM2.20, addressing key terms of binding free energy using semiempirical quantum-mechanical computational methods. SQM2.20 incorporate...
CheminformaticsComputational chemistryStructure-based drug design
10.1038/S41467-024-45431-8
ISSN:2041-1723
Novel bacterial clade reveals origin of form I Rubisco
Douglas M. Banda•Jose H. Pereira•Albert K. Liu•Douglas J. Orr•Michal Hammel等 11 人
Nature Plants
2020
•2020/8/31
•Vol.6 No.9 p.1158-1166
Rubisco sustains the biosphere through the fixation of CO2 into biomass. In plants and cyanobacteria, form I Rubisco is structurally comprised of large and small subunits, whereas all other Rubisco forms lack small subunits. The rise of the form I complex through the innovation of small subunits rep...
BiogeochemistryEvolutionRubiscoSAXSX-ray crystallography
10.1038/S41477-020-00762-4
ISSN:2055-0278
Visualization of translation and protein biogenesis at the ER membrane
Gemmer Max•Chaillet Marten L.•van Loenhout Joyce•Cuevas Arenas Rodrigo•Vismpas Dimitrios等 13 人
Nature
2023
•2023/1/25
•Vol.614 No.7946 p.160-167
The dynamic ribosome–translocon complex, which resides at the endoplasmic reticulum (ER) membrane, produces a major fraction of the human proteome1,2. It governs the synthesis, translocation, membrane insertion, N-glycosylation, folding and disulfide-bond formation of nascent proteins. Although indi...
Cryoelectron tomographyEndoplasmic reticulumRibosomal proteins
10.1038/S41586-022-05638-5
ISSN:0028-0836
Structure and function of an Arabidopsis thaliana sulfate transporter
Lie Wang•Kehan Chen•Ming Zhou
Nature Communications
2021
•2021/7/22
•Vol.12 No.1 p.1-8
Plant sulfate transporters (SULTR) mediate absorption and distribution of sulfate (SO42−) and are essential for plant growth; however, our understanding of their structures and functions remains inadequate. Here we present the structure of a SULTR from Arabidopsis thaliana, AtSULTR4;1, in complex wi...
Cryoelectron microscopyPermeation and transportPlant transporters
10.1038/S41467-021-24778-2
ISSN:2041-1723
LoCoHD: a metric for comparing local environments of proteins
Zsolt Fazekas•Dóra K. Menyhárd•András Perczel
Nature Communications
2024
•2024/5/13
•Vol.15 No.1 p.1-14
Protein folds and the local environments they create can be compared using a variety of differently designed measures, such as the root mean squared deviation, the global distance test, the template modeling score or the local distance difference test. Although these measures have proven to be usefu...
Protein analysisProtein foldingProtein structure predictionsSoftwareStatistical methods
10.1038/S41467-024-48225-0
ISSN:2041-1723
A cyclase that catalyses competing 2 + 2 and 4 + 2 cycloadditions
Wang Hongbo•Zou Yike•Li Miao•Tang Zhijun•Wang Jiabao等 13 人
Nature Chemistry
2023
•2023/1/23
•Vol.15 No.2 p.177-184
Cycloaddition reactions are among the most widely used reactions in chemical synthesis. Nature achieves these cyclization reactions with a variety of enzymes, including Diels–Alderases that catalyse concerted 4 + 2 cycloadditions, but biosynthetic enzymes with 2 + 2 cyclase activity have yet to be d...
BiocatalysisBiosynthesis
10.1038/S41557-022-01104-X
ISSN:1755-4330
Structure-guided design of partial agonists at an opioid receptor
Balazs R. Varga•Sarah M. Bernhard•Amal El Daibani•Saheem A. Zaidi•Jordy H. Lam等 21 人
Nature Communications
2025
•2025/3/13
•Vol.16 No.1 p.1-15
Chronic pain and opioid overdose deaths highlight the need for non-addictive analgesics with novel mechanisms. The δ opioid receptor (δOR) is a promising target, as it lacks the respiratory depression associated with µ opioid receptor (µOR) agonists. However, early δOR full agonists caused seizures,...
Receptor pharmacologyStructure-based drug design
10.1038/S41467-025-57734-5
ISSN:2041-1723
Molecular basis for RNA polymerase-dependent transcription complex recycling by the helicase-like motor protein HelD
Timothy P. Newing•Aaron J. Oakley•Michael Miller•Catherine J. Dawson•Simon H. J. Brown等 8 人
Nature Communications
2020
•2020/12/18
•Vol.11 No.1 p.1-11
In bacteria, transcription complexes stalled on DNA represent a major source of roadblocks for the DNA replication machinery that must be removed in order to prevent damaging collisions. Gram-positive bacteria contain a transcription factor HelD that is able to remove and recycle stalled complexes, ...
Cryoelectron microscopyEnzyme mechanismsTranscription
10.1038/S41467-020-20157-5
ISSN:2041-1723
α-Catenin levels determine direction of YAP/TAZ response to autophagy perturbation
Mariana Pavel•So Jung Park•Rebecca A. Frake•Sung Min Son•Marco M. Manni等 11 人
Nature Communications
2021
•2021/3/17
•Vol.12 No.1 p.1-21
The factors regulating cellular identity are critical for understanding the transition from health to disease and responses to therapies. Recent literature suggests that autophagy compromise may cause opposite effects in different contexts by either activating or inhibiting YAP/TAZ co-transcriptiona...
AutophagyCell biologyMacroautophagy
10.1038/S41467-021-21882-1
ISSN:2041-1723
Structural basis for abscisic acid efflux mediated by ABCG25 in Arabidopsis thaliana
Wei Ying•Lianghuan Liao•Hong Wei•Yongxiang Gao•Xin Liu等 6 人
Nature Plants
2023
•2023/9/4
•00 p.1-12
Abscisic acid (ABA) is a phytohormone essential to the regulation of numerous aspects of plant growth and development. The cellular level of ABA is critical to its signalling and is determined by its rate of biosynthesis, catabolism and the rates of ABA transport. ABCG25 in Arabidopsis thaliana has ...
Cryoelectron microscopyPlant hormones
10.1038/S41477-023-01510-0
ISSN:2055-0278
OXPHOS remodeling in high-grade prostate cancer involves mtDNA mutations and increased succinate oxidation
Bernd Schöpf•Hansi Weissensteiner•Georg Schäfer•Federica Fazzini•Pornpimol Charoentong等 17 人
Nature Communications
2020
•2020/3/20
•Vol.11 No.1 p.1-16
Rewiring of energy metabolism and adaptation of mitochondria are considered to impact on prostate cancer development and progression. Here, we report on mitochondrial respiration, DNA mutations and gene expression in paired benign/malignant human prostate tissue samples. Results reveal reduced respi...
MetabolomicsNext-generation sequencingProstate cancer
10.1038/S41467-020-15237-5
ISSN:2041-1723
Exquisite selectivity of griselimycin extends to beta subunit of DNA polymerases from Gram-negative bacterial pathogens
Michael K. Fenwick•Phillip G. Pierce•Jan Abendroth•Kayleigh F. Barrett•Lynn K. Barrett等 33 人
Communications Biology
2024
•2024/12/5
•Vol.7 No.1 p.1-13
Griselimycin, a cyclic depsidecapeptide produced by Streptomyces griseus, is a promising lead inhibitor of the sliding clamp component of bacterial DNA polymerases (β-subunit of Escherichia coli DNA pol III). It was previously shown to inhibit the Mycobacterium tuberculosis β-clamp with remarkably h...
Target identificationX-ray crystallography
10.1038/S42003-024-07175-5
ISSN:2399-3642
Computational optimization of antibody humanness and stability by systematic energy-based ranking
Ariel Tennenhouse•Lev Khmelnitsky•Razi Khalaila•Noa Yeshaya•Ashish Noronha等 15 人
Nature Biomedical Engineering
2023
•2023/8/7
•00 p.1-15
Conventional methods for humanizing animal-derived antibodies involve grafting their complementarity-determining regions onto homologous human framework regions. However, this process can substantially lower antibody stability and antigen-binding affinity, and requires iterative mutational fine-tuni...
Antibody generationProtein designProteins
10.1038/S41551-023-01079-1
ISSN:2157-846X
Structure–function and mechanistic analyses of nickel-dependent sulfonamide synthase
Yuhao Zhu•Takahiro Mori•Henrik P. H. Wong•Takayoshi Awakawa•Sam P. de Visser等 6 人
Nature Catalysis
2026
•2026/2/23
•Vol.9 No.3 p.295-306
The sulfonamide group is an important functional group in biology and medicine that shows unique chemical properties and functions and is widely used in many marketed drugs. However, insertion of a sulfonamide group into a chemical scaffold is challenging and little is known about enzymatic sulfonam...
BiocatalysisEnzyme mechanismsStructural biology
10.1038/S41929-026-01493-Z
ISSN:2520-1158
Pharmacological targeting of BMAL1 modulates circadian and immune pathways
Hua Pu•Laura C. Bailey•Ludwig G. Bauer•Maria Voronkov•Matthew Baxter等 9 人
Nature Chemical Biology
2025
•2025/3/25
•00 p.1-10
The basic helix–loop–helix PER-ARNT-SIM (bHLH-PAS) proteins BMAL1 and CLOCK heterodimerize to form the master transcription factor governing rhythmic gene expression. Owing to connections between circadian regulation and numerous physiological pathways, targeting the BMAL1–CLOCK complex pharmacologi...
Biophysical chemistryCircadian rhythmsPharmacologySmall moleculesTarget identification
10.1038/S41589-025-01863-X
ISSN:1552-4450
A novel class of inhibitors that disrupts the stability of integrin heterodimers identified by CRISPR-tiling-instructed genetic screens
Nicole M. Mattson•Anthony K. N. Chan•Kazuya Miyashita•Elizaveta Mukhaleva•Wen-Han Chang等 27 人
Nature Structural & Molecular Biology
2024
•2024/2/5
•00 p.1-11
The plasma membrane is enriched for receptors and signaling proteins that are accessible from the extracellular space for pharmacological intervention. Here we conducted a series of CRISPR screens using human cell surface proteome and integrin family libraries in multiple cancer models. Our results ...
CancerDrug discoveryHigh-throughput screening
10.1038/S41594-024-01211-Y
ISSN:1545-9993
The cryo-EM structure of the human neurofibromin dimer reveals the molecular basis for neurofibromatosis type 1
Lupton Christopher J.•Bayly-Jones Charles•D’Andrea Laura•Huang Cheng•Schittenhelm Ralf B.等 9 人
Nature Structural & Molecular Biology
2021
•2021/12/9
•Vol.28 No.12 p.982-988
Neurofibromin (NF1) mutations cause neurofibromatosis type 1 and drive numerous cancers, including breast and brain tumors. NF1 inhibits cellular proliferation through its guanosine triphosphatase-activating protein (GAP) activity against rat sarcoma (RAS). In the present study, cryo-electron micros...
Cryoelectron microscopyTumour-suppressor proteins
10.1038/S41594-021-00687-2
ISSN:1545-9993
Commercial influenza vaccines vary in HA-complex structure and in induction of cross-reactive HA antibodies
Myers Mallory L.•Gallagher John R.•Kim Alexander J.•Payne Walker H.•Maldonado-Puga Samantha等 10 人
Nature Communications
2023
•2023/3/30
•Vol.14 No.1 p.1-15
Influenza virus infects millions of people annually and can cause global pandemics. Hemagglutinin (HA) is the primary component of commercial influenza vaccines (CIV), and antibody titer to HA is a primary correlate of protection. Continual antigenic variation of HA requires that CIVs are reformulat...
Cryoelectron tomographyInfluenza virusVaccines
10.1038/S41467-023-37162-Z
ISSN:2041-1723
Accurate RNA 3D structure prediction using a language model-based deep learning approach
Tao Shen•Zhihang Hu•Siqi Sun•Di Liu•Felix Wong等 17 人
Nature Methods
2024
•2024/11/21
•00 p.1-12
Accurate prediction of RNA three-dimensional (3D) structures remains an unsolved challenge. Determining RNA 3D structures is crucial for understanding their functions and informing RNA-targeting drug development and synthetic biology design. The structural flexibility of RNA, which leads to the scar...
Computational biology and bioinformaticsMachine learningRNA
10.1038/S41592-024-02487-0
ISSN:1548-7091
Real-time observation of a metal complex-driven reaction intermediate using a porous protein crystal and serial femtosecond crystallography
Basudev Maity•Mitsuo Shoji•Fangjia Luo•Takanori Nakane•Satoshi Abe等 24 人
Nature Communications
2024
•2024/6/29
•Vol.15 No.1 p.1-12
Determining short-lived intermediate structures in chemical reactions is challenging. Although ultrafast spectroscopic methods can detect the formation of transient intermediates, real-space structures cannot be determined directly from such studies. Time-resolved serial femtosecond crystallography ...
Chemical bondingCrystal engineeringX-ray crystallography
10.1038/S41467-024-49814-9
ISSN:2041-1723
Crystal structure of the mitochondrial protein mitoNEET bound to a benze-sulfonide ligand
Werner J. Geldenhuys•Timothy E. Long•Pushkar Saralkar•Toshio Iwasaki•Raisa A. A. Nuñez等 12 人
Communications Chemistry
2019
•2019/7/3
•Vol.2 No.1 p.1-9
MitoNEET (gene cisd1) is a mitochondrial outer membrane [2Fe-2S] protein and is a potential drug target in several metabolic diseases. Previous studies have demonstrated that mitoNEET functions as a redox-active and pH-sensing protein that regulates mitochondrial metabolism, although the structural ...
Drug discoveryStructural biology
10.1038/S42004-019-0172-X
ISSN:2399-3669
Molecular basis of differential HLA class I-restricted T cell recognition of a highly networked HIV peptide
Xiaolong Li•Nishant Kumar Singh•David R. Collins•Robert Ng•Angela Zhang等 21 人
Nature Communications
2023
•2023/5/22
•Vol.14 No.1 p.1-15
Cytotoxic-T-lymphocyte (CTL) mediated control of HIV-1 is enhanced by targeting highly networked epitopes in complex with human-leukocyte-antigen-class-I (HLA-I). However, the extent to which the presenting HLA allele contributes to this process is unknown. Here we examine the CTL response to QW9, a...
Cellular immunityCytotoxic T cellsHIV infectionsImmunological memoryX-ray crystallography
10.1038/S41467-023-38573-8
ISSN:2041-1723
Time-resolved crystallography of boric acid binding to the active site serine of the β-lactamase CTX-M-14 and subsequent 1,2-diol esterification
Andreas Prester•Markus Perbandt•Marina Galchenkova•Dominik Oberthuer•Nadine Werner等 16 人
Communications Chemistry
2024
•2024/7/5
•Vol.7 No.1 p.1-12
The emergence and spread of antibiotic resistance represent a growing threat to public health. Of particular concern is the appearance of β-lactamases, which are capable to hydrolyze and inactivate the most important class of antibiotics, the β-lactams. Effective β-lactamase inhibitors and mechanist...
Enzyme mechanismsMechanism of actionX-ray crystallography
10.1038/S42004-024-01236-W
ISSN:2399-3669
Multi-interface licensing of protein import into a phage nucleus
Claire Kokontis•Timothy A. Klein•Sukrit Silas•Joseph Bondy-Denomy
Nature
2025
•2025/2/5
•Vol.639 No.8054 p.456-462
Bacteriophages use diverse mechanisms to evade antiphage defence systems. ΦKZ-like jumbo phages assemble a proteinaceous, nucleus-like compartment that excludes antagonistic host nucleases and also internalizes DNA replication and transcription machinery1–4. The phage factors required for protein im...
BacteriologyBacteriophages
10.1038/S41586-024-08547-X
ISSN:0028-0836
Structural dissimilarity from self drives neoepitope escape from immune tolerance
Jason R. Devlin•Jesus A. Alonso•Cory M. Ayres•Grant L. J. Keller•Sara Bobisse等 10 人
Nature Chemical Biology
2020
•2020/8/17
•Vol.16 No.11 p.1269-1276
T-cell recognition of peptides incorporating nonsynonymous mutations, or neoepitopes, is a cornerstone of tumor immunity and forms the basis of new immunotherapy approaches including personalized cancer vaccines. Yet as they are derived from self-peptides, the means through which immunogenic neoepit...
Biophysical chemistryImmunologyVaccinesX-ray crystallography
10.1038/S41589-020-0610-1
ISSN:1552-4450
Substrate binding and catalytic mechanism of the Se-glycosyltransferase SenB in the biosynthesis of selenoneine
Wei Huang•Jun Song•Tianxue Sun•Yue He•Xiang Li等 7 人
Nature Communications
2024
•2024/2/23
•Vol.15 No.1 p.1-10
Selenium is an essential multifunctional trace element in diverse organisms. The only Se-glycosyltransferase identified that catalyzes the incorporation of selenium in selenoneine biosynthesis is SenB from Variovorax paradoxus. Although the biochemical function of SenB has been investigated, its sub...
Enzyme mechanismsGlycobiologyMetalsX-ray crystallography
10.1038/S41467-024-46065-6
ISSN:2041-1723
Molecular basis for carrier protein-dependent amide bond formation in the biosynthesis of lincosamide antibiotics
Takahiro Mori•Stanislav Kadlcik•Shuang Lyu•Zdenek Kamenik•Kosuke Sakurada等 9 人
Nature Catalysis
2023
•2023/6/12
•Vol.6 No.6 p.531-542
In the biosynthesis of the lincosamide antibiotic celesticetin, the condensation enzyme CcbD generates the lincosamide pharmacophore by forming an amide bond between the carrier protein (CP)-tethered proline and ergothioneine-conjugated thiooctose. Although the function of CcbD has been investigated...
AntibioticsBiosynthesisEnzyme mechanismsNatural productsX-ray crystallography
10.1038/S41929-023-00971-Y
ISSN:2520-1158
IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation
Fuqing Hu•Da Song•Yumeng Yan•Changsheng Huang•Chentao Shen等 18 人
Nature Communications
2021
•2021/6/15
•Vol.12 No.1 p.1-14
Extracellular cytokines are enriched in the tumor microenvironment and regulate various important properties of cancers, including autophagy. However, the precise molecular mechanisms underlying the link between autophagy and extracellular cytokines remain to be elucidated. In the present study, we ...
Cancer therapeutic resistancePhosphorylation
10.1038/S41467-021-23923-1
ISSN:2041-1723
Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH
Stsiapanava Alena•Xu Chenrui•Nishio Shunsuke•Han Ling•Yamakawa Nao等 11 人
Nature Structural & Molecular Biology
2022
•2022/3/10
•00 p.1-4
Glycoprotein 2 (GP2) and uromodulin (UMOD) filaments protect against gastrointestinal and urinary tract infections by acting as decoys for bacterial fimbrial lectin FimH. By combining AlphaFold2 predictions with X-ray crystallography and cryo-EM, we show that these proteins contain a bipartite decoy...
Cryoelectron microscopyGlycoproteinsMolecular modellingX-ray crystallography
10.1038/S41594-022-00729-3
ISSN:1545-9993
Broadly therapeutic antibody provides cross-serotype protection against enteroviruses via Fc effector functions and by mimicking SCARB2
Rui Zhu•Yuanyuan Wu•Yang Huang•Yanan Jiang•Yichao Jiang等 34 人
Nature Microbiology
2024
•2024/10/18
•00 p.1-15
Enteroviruses contain multiple serotypes and can cause severe neurological complications. The intricate life cycle of enteroviruses involving dynamic virus–receptor interaction hampers the development of broad therapeutics and vaccines. Here, using function-based screening, we identify a broadly the...
Electron microscopyTarget identificationVirology
10.1038/S41564-024-01822-7
ISSN:2058-5276
Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome
Barry Alexandra•McNulty Michelle T.•Jia Xiaoyuan•Gupta Yask•Debiec Hanna等 70 人
Nature Communications
2023
•2023/4/29
•Vol.14 No.1 p.1-13
Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its geneti...
GeneticsMinimal change diseasePaediatric kidney disease
10.1038/S41467-023-37985-W
ISSN:2041-1723
Structural basis of lipid-droplet localization of 17-beta-hydroxysteroid dehydrogenase 13
Shenping Liu•Ruth F. Sommese•Nicole L. Nedoma•Lucy Mae Stevens•Jason K. Dutra等 10 人
Nature Communications
2023
•2023/8/24
•Vol.14 No.1 p.1-14
Hydroxysteroid 17-beta-dehydrogenase 13 (HSD17B13) is a hepatic lipid droplet-associated enzyme that is upregulated in patients with non-alcoholic fatty liver disease. Recently, there have been several reports that predicted loss of function variants in HSD17B13 protect against the progression of st...
Membrane structure and assemblyStructure-based drug designX-ray crystallography
10.1038/S41467-023-40766-0
ISSN:2041-1723
Rational design of uncleaved prefusion-closed trimer vaccines for human respiratory syncytial virus and metapneumovirus
Yi-Zong Lee•Jerome Han•Yi-Nan Zhang•Garrett Ward•Keegan Braz Gomes等 10 人
Nature Communications
2024
•2024/11/16
•Vol.15 No.1 p.1-25
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause human respiratory diseases and are major targets for vaccine development. In this study, we design uncleaved prefusion-closed (UFC) trimers for the fusion protein (F) of both viruses by examining mutations critical to F metasta...
Protein vaccinesVirologyX-ray crystallography
10.1038/S41467-024-54287-X
ISSN:2041-1723
Protein complex prediction using Rosetta, AlphaFold, and mass spectrometry covalent labeling
Drake Zachary C.•Seffernick Justin T.•Lindert Steffen
Nature Communications
2022
•2022/12/21
•Vol.13 No.1 p.1-9
Covalent labeling (CL) in combination with mass spectrometry can be used as an analytical tool to study and determine structural properties of protein-protein complexes. However, data from these experiments is sparse and does not unambiguously elucidate protein structure. Thus, computational algorit...
Computational biophysicsMass spectrometryProtein structure predictions
10.1038/S41467-022-35593-8
ISSN:2041-1723
Substrate promiscuity of inositol 1,4,5-trisphosphate kinase driven by structurally-modified ligands and active site plasticity
María Ángeles Márquez-Moñino•Raquel Ortega-García•Hayley Whitfield•Andrew M. Riley•Lourdes Infantes等 10 人
Nature Communications
2024
•2024/2/19
•Vol.15 No.1 p.1-16
d-myo-inositol 1,4,5-trisphosphate (InsP3) is a fundamental second messenger in cellular Ca2+ mobilization. InsP3 3-kinase, a highly specific enzyme binding InsP3 in just one mode, phosphorylates InsP3 specifically at its secondary 3-hydroxyl group to generate a tetrakisphosphate. Using a chemical b...
KinasesScreeningSmall moleculesStructural biologyX-ray crystallography
10.1038/S41467-024-45917-5
ISSN:2041-1723
Direct-acting antiviral resistance of Hepatitis C virus is promoted by epistasis
Hang Zhang•Ahmed Abdul Quadeer•Matthew R. McKay
Nature Communications
2023
•2023/11/17
•Vol.14 No.1 p.1-14
Direct-acting antiviral agents (DAAs) provide efficacious therapeutic treatments for chronic Hepatitis C virus (HCV) infection. However, emergence of drug resistance mutations (DRMs) can greatly affect treatment outcomes and impede virological cure. While multiple DRMs have been observed for all cur...
Computational biology and bioinformaticsHepatitis CHepatitis C virusStatistical physics
10.1038/S41467-023-42550-6
ISSN:2041-1723
TRIM66 reads unmodified H3R2K4 and H3K56ac to respond to DNA damage in embryonic stem cells
Jiajing Chen•Zikang Wang•Xudong Guo•Fudong Li•Qingtao Wei等 12 人
Nature Communications
2019
•2019/9/19
•Vol.10 No.1 p.1-17
Recognition of specific chromatin modifications by distinct structural domains within “reader” proteins plays a critical role in the maintenance of genomic stability. However, the specific mechanisms involved in this process remain unclear. Here we report that the PHD-Bromo tandem domain of triparti...
DNA damage and repairEmbryonic stem cellsStructural biology
10.1038/S41467-019-12126-4
ISSN:2041-1723
Peptide design through binding interface mimicry with PepMimic
Xiangzhe Kong•Rui Jiao•Haowei Lin•Ruihan Guo•Wenbing Huang等 9 人
Nature Biomedical Engineering
2025
•2025/10/1
•00 p.1-16
Peptides offer advantages for targeted therapy, including oral bioavailability, cellular permeability and high specificity, setting them apart from conventional small molecules and biologics. Here we develop an artificial intelligence algorithm, PepMimic, to transform a known receptor or an existing...
Machine learningPeptides
10.1038/S41551-025-01507-4
ISSN:2157-846X
HPF1 remodels the active site of PARP1 to enable the serine ADP-ribosylation of histones
Fa-Hui Sun•Peng Zhao•Nan Zhang•Lu-Lu Kong•Catherine C. L. Wong等 6 人
Nature Communications
2021
•2021/2/15
•Vol.12 No.1 p.1-10
Upon binding to DNA breaks, poly(ADP-ribose) polymerase 1 (PARP1) ADP-ribosylates itself and other factors to initiate DNA repair. Serine is the major residue for ADP-ribosylation upon DNA damage, which strictly depends on HPF1. Here, we report the crystal structures of human HPF1/PARP1-CAT ΔHD comp...
DNA damage responseX-ray crystallography
10.1038/S41467-021-21302-4
ISSN:2041-1723
Structural basis for the evolution and antibody evasion of SARS-CoV-2 BA.2.86 and JN.1 subvariants
Haonan Yang•Huimin Guo•Aojie Wang•Liwei Cao•Qing Fan等 15 人
Nature Communications
2024
•2024/9/4
•Vol.15 No.1 p.1-14
The Omicron subvariants of SARS-CoV-2, especially for BA.2.86 and JN.1, have rapidly spread across multiple countries, posing a significant threat in the ongoing COVID-19 pandemic. Distinguished by 34 additional mutations on the Spike (S) protein compared to its BA.2 predecessor, the implications of...
Antimicrobial responsesSARS-CoV-2Structural biology
10.1038/S41467-024-51973-8
ISSN:2041-1723
Conformational trajectory of the HIV-1 fusion peptide during CD4-induced envelope opening
Bhishem Thakur•Revansiddha H. Katte•Wang Xu•Katarzyna Janowska•Salam Sammour等 9 人
Nature Communications
2025
•2025/5/17
•Vol.16 No.1 p.1-14
The hydrophobic fusion peptide (FP), a critical component of the HIV-1 entry machinery, is located at the N terminus of the envelope (Env) gp41 subunit. The receptor-binding gp120 subunit of Env forms a heterodimer with gp41. The gp120/gp41 heterodimer assembles into a homotrimer, in which FP is acc...
Cryoelectron microscopyHIV infections
10.1038/S41467-025-59721-2
ISSN:2041-1723
Structural basis for the assembly and translocation of the Vip1-Vip2 insecticidal toxin from Bacillus thuringiensis
Ting Zhao•Zeyu Wang•Jing Ren•Xianle Han•Linpeng Li等 8 人
Nature Communications
2026
•2026/3/30
0Insecticidal toxins from Bacillus thuringiensis (Bt) have been extensively and successfully used in genetically engineered crops for decades but continue to face challenges from the adaptive resistance in the insect population. The Bt binary toxin Vip1Ad1(Vip1) and Vip2Ag1(Vip2), a promising next-ge...
Bacterial structural biologyBacterial toxinsCryoelectron microscopy
10.1038/S41467-026-71211-7
ISSN:2041-1723
Structural surfaceomics reveals an AML-specific conformation of integrin β2 as a CAR T cellular therapy target
Kamal Mandal•Gianina Wicaksono•Clinton Yu•Jarrett J. Adams•Michael R. Hoopmann等 36 人
Nature Cancer
2023
•2023/10/30
•00 p.1-18
Safely expanding indications for cellular therapies has been challenging given a lack of highly cancer-specific surface markers. Here we explore the hypothesis that tumor cells express cancer-specific surface protein conformations that are invisible to standard target discovery pipelines evaluating ...
Acute myeloid leukaemiaCancerCancer immunotherapyProteomics
10.1038/S43018-023-00652-6
ISSN:2662-1347
Enabling target-aware molecule generation to follow multi objectives with Pareto MCTS
Yaodong Yang•Guangyong Chen•Jinpeng Li•Junyou Li•Odin Zhang等 10 人
Communications Biology
2024
•2024/9/2
•Vol.7 No.1 p.1-15
Target-aware drug discovery has greatly accelerated the drug discovery process to design small-molecule ligands with high binding affinity to disease-related protein targets. Conditioned on targeted proteins, previous works utilize various kinds of deep generative models and have shown great potenti...
Computational modelsPharmaceutics
10.1038/S42003-024-06746-W
ISSN:2399-3642
Structural basis of ion transport and inhibition in ferroportin
Yaping Pan•Zhenning Ren•Shuai Gao•Jiemin Shen•Lie Wang等 13 人
Nature Communications
2020
•2020/11/10
•Vol.11 No.1 p.1-11
Ferroportin is an iron exporter essential for releasing cellular iron into circulation. Ferroportin is inhibited by a peptide hormone, hepcidin. In humans, mutations in ferroportin lead to ferroportin diseases that are often associated with accumulation of iron in macrophages and symptoms of iron de...
Cryoelectron microscopyProteins
10.1038/S41467-020-19458-6
ISSN:2041-1723
Accelerating reliable multiscale quantum refinement of protein–drug systems enabled by machine learning
Zeyin Yan•Dacong Wei•Xin Li•Lung Wa Chung
Nature Communications
2024
•2024/5/16
•Vol.15 No.1 p.1-12
Biomacromolecule structures are essential for drug development and biocatalysis. Quantum refinement (QR) methods, which employ reliable quantum mechanics (QM) methods in crystallographic refinement, showed promise in improving the structural quality or even correcting the structure of biomacromolecu...
Computational chemistryProteinsStructure predictionX-ray crystallography
10.1038/S41467-024-48453-4
ISSN:2041-1723
Mosaic composition of RIP1–RIP3 signalling hub and its role in regulating cell death
Chen Xin•Zhu Rongfeng•Zhong Jinjin•Ying Yongfa•Wang Wenxin等 10 人
Nature Cell Biology
2022
•2022/3/7
•00 p.1-12
RIP1 and RIP3, cell death mediators, form fibrous amyloids. How RIP1/RIP3 amyloidal oligomers assemble functional necrosomes and control cell death is largely unknown. Here we use super-resolution microscopy to directly visualize cellular necrosomes as mosaics of RIP1 and RIP3 oligomers. The small (...
Cell signallingNecroptosisSuper-resolution microscopy
10.1038/S41556-022-00854-7
ISSN:1465-7392
Structural basis for potent neutralization of human respirovirus type 3 by protective single-domain camelid antibodies
Nicole V. Johnson•Revina C. van Scherpenzeel•Mark J. G. Bakkers•Ajit R. Ramamohan•Daan van Overveld等 9 人
Nature Communications
2024
•2024/6/27
•Vol.15 No.1 p.1-14
Respirovirus 3 is a leading cause of severe acute respiratory infections in vulnerable human populations. Entry into host cells is facilitated by the attachment glycoprotein and the fusion glycoprotein (F). Because of its crucial role, F represents an attractive therapeutic target. Here, we identify...
AntibodiesCryoelectron microscopyViral infectionVirology
10.1038/S41467-024-49757-1
ISSN:2041-1723
Cryo-electron microscopy reveals two distinct type IV pili assembled by the same bacterium
Alexander Neuhaus•Muniyandi Selvaraj•Ralf Salzer•Julian D. Langer•Kerstin Kruse等 10 人
Nature Communications
2020
•2020/5/6
•Vol.11 No.1 p.1-13
Type IV pili are flexible filaments on the surface of bacteria, consisting of a helical assembly of pilin proteins. They are involved in bacterial motility (twitching), surface adhesion, biofilm formation and DNA uptake (natural transformation). Here, we use cryo-electron microscopy and mass spectro...
Bacterial structural biologyCellular microbiologyCryoelectron microscopy
10.1038/S41467-020-15650-W
ISSN:2041-1723
Structural basis for transthiolation intermediates in the ubiquitin pathway
Tomasz Kochańczyk•Zachary S. Hann•Michaelyn C. Lux•Avelyn Mae V. Delos Reyes•Cheng Ji等 7 人
Nature
2024
•2024/8/14
•00 p.1-8
Transthiolation (also known as transthioesterification) reactions are used in the biosynthesis of acetyl coenzyme A, fatty acids and polyketides, and for post-translational modification by ubiquitin (Ub) and ubiquitin-like (Ubl) proteins1–3. For the Ub pathway, E1 enzymes catalyse transthiolation fr...
Cryoelectron microscopyEnzyme mechanisms
10.1038/S41586-024-07828-9
ISSN:0028-0836
Predicting protein function and orientation on a gold nanoparticle surface using a residue-based affinity scale
Xu Joanna Xiuzhu•Alom Md. Siddik•Yadav Rahul•Fitzkee Nicholas C.
Nature Communications
2022
•2022/11/27
•Vol.13 No.1 p.1-11
The orientation adopted by proteins on nanoparticle surfaces determines the nanoparticle’s bioactivity and its interactions with living systems. Here, we present a residue-based affinity scale for predicting protein orientation on citrate-gold nanoparticles (AuNPs). Competitive binding between prote...
Molecular conformationNanoparticlesSolution-state NMR
10.1038/S41467-022-34749-W
ISSN:2041-1723
Structural basis for the multi-activity factor Rad5 in replication stress tolerance
Miaomiao Shen•Nalini Dhingra•Quan Wang•Chen Cheng•Songbiao Zhu等 19 人
Nature Communications
2021
•2021/1/12
•Vol.12 No.1 p.1-12
The yeast protein Rad5 and its orthologs in other eukaryotes promote replication stress tolerance and cell survival using their multiple activities, including ubiquitin ligase, replication fork remodeling and DNA lesion targeting activities. Here, we present the crystal structure of a nearly full-le...
BiochemistryStalled forksUbiquitylationX-ray crystallography
10.1038/S41467-020-20538-W
ISSN:2041-1723
The ISC machinery assembles [2Fe–2S] clusters by formation and fusion of [1Fe–1S] precursors
Sylvain Gervason•Rafal Dutkiewicz•Kristian Want•Rania Benazza•Rémi Mor-Gautier等 12 人
Nature Chemical Biology
2025
•2025/1/27
•00 p.1-12
Iron–sulfur clusters are essential metallocofactors synthesized by multiprotein machineries via an unclear multistep process. Here we report a step-by-step dissection of the [2Fe–2S] cluster assembly process by the Escherichia coli iron–sulfur cluster (ISC) assembly machinery using an in vitro recon...
BiophysicsEnzyme mechanismsMass spectrometryMetalloproteinsMetals
10.1038/S41589-024-01818-8
ISSN:1552-4450
Ferricyanide-mediated direct ligation of peptide hydrazides in neutral water
Dongyang Han•Xianglai Zhu•Guiyu Deng•Wei He•Tianyi Zhang等 8 人
Nature Synthesis
2026
•2026/7/24
•00 p.1-12
Hydrazide-based native chemical ligation has emerged as one of the most widely used methods in modern chemical protein synthesis, but its traditional two-step, dual-environment workflow complicates operations and limits small-scale reactions. Here we present a ferricyanide-mediated system that enabl...
Synthetic chemistry methodologyPeptidesSynthetic biology
10.1038/S44160-026-01121-5
ISSN:2731-0582
HPF1 dynamically controls the PARP1/2 balance between initiating and elongating ADP-ribose modifications
Langelier Marie-France•Billur Ramya•Sverzhinsky Aleksandr•Black Ben E.•Pascal John M.
Nature Communications
2021
•2021/11/18
•Vol.12 No.1 p.1-14
PARP1 and PARP2 produce poly(ADP-ribose) in response to DNA breaks. HPF1 regulates PARP1/2 catalytic output, most notably permitting serine modification with ADP-ribose. However, PARP1 is substantially more abundant in cells than HPF1, challenging whether HPF1 can pervasively modulate PARP1. Here, w...
Enzyme mechanismsPolyADP-ribosylationStructural biology
10.1038/S41467-021-27043-8
ISSN:2041-1723
Discovery of the selenium-containing antioxidant ovoselenol derived from convergent evolution
Chase M. Kayrouz•Kendra A. Ireland•Vanessa Y. Ying•Katherine M. Davis•Mohammad R. Seyedsayamdost
Nature Chemistry
2024
•2024/8/14
•00 p.1-8
Selenium is an essential micronutrient, but its presence in biology has been limited to protein and nucleic acid biopolymers. The recent identification of a biosynthetic pathway for selenium-containing small molecules suggests that there is a larger family of selenometabolites that remains to be dis...
BiosynthesisOxidoreductasesX-ray crystallography
10.1038/S41557-024-01600-2
ISSN:1755-4330
Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants
Yu Haisheng•Liu Banghui•Zhang Yudi•Gao Xijie•Wang Qian等 39 人
Nature Communications
2023
•2023/2/24
•Vol.14 No.1 p.1-14
SARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier in the pandemic. Investigation of memory B cells from patients primarily with breakthrough infections with the Delta variant enables isolation of a number of neutrali...
Cryoelectron microscopyInactivated vaccinesSARS-CoV-2Somatic hypermutation
10.1038/S41467-023-36761-0
ISSN:2041-1723
Atomic structure and in situ visualization of native PMEL lamellae in melanosomes
Boyuan Ma•Yuxuan Yao•Hui Dong•Linli Yang•Danni Li等 10 人
Nature Communications
2025
•2025/11/21
•Vol.16 No.1 p.103000
Melanin synthesis within melanosomes critically depends on the fibrillar architecture formed by the pigment cell-specific protein PMEL. Although PMEL fibrils have historically been classified as functional amyloids, their native supramolecular organization in situ and detailed molecular architecture...
BiochemistryBiophysicsCryoelectron microscopyCryoelectron tomographyOrganelles
10.1038/S41467-025-65221-0
ISSN:2041-1723
Discovery of a distinct type of methylenetetrahydrofolate reductase family that couples with tetrahydrofolate-dependent demethylases
HongYang Yu•Naofumi Kamimura•Ryo Kato•Michelle Jane Genoveso•Miki Senda等 7 人
Communications Biology
2025
•2025/2/27
•Vol.8 No.1 p.1-11
Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in one-carbon (1C) metabolism, catalyzing the reduction of methylenetetrahydrofolate to methyltetrahydrofolate. Interestingly, Sphingobium lignivorans SYK-6, a model bacterium for the catabolism of lignin-derived aromatic compounds, possess...
Applied microbiologyX-ray crystallography
10.1038/S42003-025-07762-0
ISSN:2399-3642
The molecular basis underlying T cell specificity towards citrullinated epitopes presented by HLA-DR4
Tiing Jen Loh•Jia Jia Lim•Claerwen M. Jones•Hien Thy Dao•Mai T. Tran等 9 人
Nature Communications
2024
•2024/7/23
•Vol.15 No.1 p.1-17
CD4+ T cells recognising citrullinated self-epitopes presented by HLA-DRB1 bearing the shared susceptibility epitope (SE) are implicated in rheumatoid arthritis (RA). However, the underlying T cell receptor (TCR) determinants of epitope specificity towards distinct citrullinated peptide antigens, in...
Adaptive immunityAutoimmunityCD4-positive T cellsLymphocyte differentiationX-ray crystallography
10.1038/S41467-024-50511-W
ISSN:2041-1723
Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus
Rivera-Calzada Angel•Arribas-Bosacoma Raquel•Ruiz-Ramos Alba•Escudero-Bravo Paloma•Boskovic Jasminka等 9 人
Nature Communications
2022
•2022/11/18
•Vol.13 No.1 p.1-13
Detection of cytosolic DNA is a central element of the innate immunity system against viral infection. The Ku heterodimer, a component of the NHEJ pathway of DNA repair in the nucleus, functions as DNA sensor that detects dsDNA of viruses that replicate in the cytoplasm. Vaccinia virus expresses two...
DNA damage and repairElectron microscopyVirology
10.1038/S41467-022-34843-Z
ISSN:2041-1723
An artificial metabzyme for tumour-cell-specific metabolic therapy
Xi Hu•Bo Zhang•Miao Zhang•Wenshi Liang•Bangzhen Hong等 14 人
Nature Nanotechnology
2024
•2024/8/5
•00 p.1-11
Metabolic dysregulation constitutes a pivotal feature of cancer progression. Enzymes with multiple metal active sites play a major role in this process. Here we report the first metabolic-enzyme-like FeMoO4 nanocatalyst, dubbed ‘artificial metabzyme’. It showcases dual active centres, namely, Fe2+ a...
NanoparticlesNanotechnology in cancer
10.1038/S41565-024-01733-Y
ISSN:1748-3387
N-terminal tyrosine of ISCU2 triggers [2Fe-2S] cluster synthesis by ISCU2 dimerization
Freibert Sven-A.•Boniecki Michal T.•Stümpfig Claudia•Schulz Vinzent•Krapoth Nils等 10 人
Nature Communications
2021
•2021/11/25
•Vol.12 No.1 p.1-15
Synthesis of iron-sulfur (Fe/S) clusters in living cells requires scaffold proteins for both facile synthesis and subsequent transfer of clusters to target apoproteins. The human mitochondrial ISCU2 scaffold protein is part of the core ISC (iron-sulfur cluster assembly) complex that synthesizes a br...
Enzyme mechanismsMitochondriaMitochondrial proteinsX-ray crystallography
10.1038/S41467-021-27122-W
ISSN:2041-1723
Crystal structures of AztD provide mechanistic insights into direct zinc transfer between proteins
Durga Prasad Neupane•Stephanie Hope Fullam•Kelly Natalia Chacón•Erik Thomas Yukl
Communications Biology
2019
•2019/8/9
•Vol.2 No.1 p.1-12
Zinc acquisition from limited environments is critical for bacterial survival and pathogenesis. AztD has been identified as a periplasmic or cell surface zinc-binding protein in numerous bacterial species. In Paracoccus denitrificans, AztD can transfer zinc directly to AztC, the solute binding prote...
MetalsX-ray crystallography
10.1038/S42003-019-0542-Z
ISSN:2399-3642
Hemipiperazines as peptide-derived molecular photoswitches with low-nanomolar cytotoxicity
Kirchner Susanne•Leistner Anna-Lena•Gödtel Peter•Seliwjorstow Angelika•Weber Sven等 8 人
Nature Communications
2022
•2022/10/14
•Vol.13 No.1 p.1-14
Molecular photoswitches transform light energy into reversible structural changes. Their combination with known pharmacophores often allows for photomodulation of the biological activity. The effort to apply such compounds in photopharmacology as light-activated pro-drugs is, however, hampered by se...
Drug deliverySingle-molecule fluorescenceSmall moleculesTargeted therapies
10.1038/S41467-022-33750-7
ISSN:2041-1723
Structural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage
Rory Henderson•Ye Zhou•Victoria Stalls•Kevin Wiehe•Kevin O. Saunders等 14 人
Nature Communications
2023
•2023/5/15
•Vol.14 No.1 p.1-17
Antibody affinity maturation enables adaptive immune responses to a wide range of pathogens. In some individuals broadly neutralizing antibodies develop to recognize rapidly mutating pathogens with extensive sequence diversity. Vaccine design for pathogens such as HIV-1 and influenza has therefore f...
Cryoelectron microscopyRetrovirusVaccines
10.1038/S41467-023-38108-1
ISSN:2041-1723
Proper chromosome alignment depends on BRCA2 phosphorylation by PLK1
Åsa Ehlén•Charlotte Martin•Simona Miron•Manon Julien•François-Xavier Theillet等 13 人
Nature Communications
2020
•2020/4/14
•Vol.11 No.1 p.1-21
The BRCA2 tumor suppressor protein is involved in the maintenance of genome integrity through its role in homologous recombination. In mitosis, BRCA2 is phosphorylated by Polo-like kinase 1 (PLK1). Here we describe how this phosphorylation contributes to the control of mitosis. We identify a conserv...
Chromosome segregationKinetochoresTumour-suppressor proteins
10.1038/S41467-020-15689-9
ISSN:2041-1723
Crowdsourced mapping of unexplored target space of kinase inhibitors
Anna Cichońska•Balaguru Ravikumar•Robert J. Allaway•Fangping Wan•Sungjoon Park等 27 人
Nature Communications
2021
•2021/6/3
•Vol.12 No.1 p.1-18
Despite decades of intensive search for compounds that modulate the activity of particular protein targets, a large proportion of the human kinome remains as yet undrugged. Effective approaches are therefore required to map the massive space of unexplored compound–kinase interactions for novel and p...
CheminformaticsKinasesMachine learning
10.1038/S41467-021-23165-1
ISSN:2041-1723
Molecular insights into the unusually promiscuous and catalytically versatile Fe(II)/α-ketoglutarate-dependent oxygenase SptF
Tao Hui•Mori Takahiro•Chen Heping•Lyu Shuang•Nonoyama Akihito等 7 人
Nature Communications
2022
•2022/1/10
•Vol.13 No.1 p.1-13
Non-heme iron and α-ketoglutarate-dependent (Fe/αKG) oxygenases catalyze various oxidative biotransformations. Due to their catalytic flexibility and high efficiency, Fe/αKG oxygenases have attracted keen attention for their application as biocatalysts. Here, we report the biochemical and structural...
BiosynthesisEnzyme mechanisms
10.1038/S41467-021-27636-3
ISSN:2041-1723
Pan-Peptide Meta Learning for T-cell receptor–antigen binding recognition
Gao Yicheng•Gao Yuli•Fan Yuxiao•Zhu Chengyu•Wei Zhiting等 10 人
Nature Machine Intelligence
2023
•2023/3/6
•Vol.5 No.3 p.236-249
The identification of the mechanisms by which T-cell receptors (TCRs) interact with human antigens provides a crucial opportunity to develop new vaccines, diagnostics and immunotherapies. However, the accurate prediction and recognition of TCR–antigen pairing represents a substantial computational c...
Computational modelsMachine learning
10.1038/S42256-023-00619-3
ISSN:2522-5839
Short prokaryotic Argonautes provide defence against incoming mobile genetic elements through NAD+ depletion
Zaremba Mindaugas•Dakineviciene Donata•Golovinas Edvardas•Zagorskaitė Evelina•Stankunas Edvinas等 18 人
Nature Microbiology
2022
•2022/10/3
•Vol.7 No.11 p.1857-1869
Argonaute (Ago) proteins are found in all three domains of life. The so-called long Agos are composed of four major domains (N, PAZ, MID and PIWI) and contribute to RNA silencing in eukaryotes (eAgos) or defence against invading mobile genetic elements in prokaryotes (pAgos). The majority (~60%) of ...
Bacterial host responseBacteriophagesEnzymesMetabolomics
10.1038/S41564-022-01239-0
ISSN:2058-5276
A SARS-CoV-2 Mpro mutation conferring ensitrelvir resistance paradoxically increases nirmatrelvir susceptibility
Seong Cheol Min•Jin-Ju Seo•Ju Hwan Jeong•Beom Kyu Kim•Ji-Hyun Park等 17 人
Nature Communications
2025
•2025/11/22
0SARS-CoV-2 variants resistant to current antivirals remain a significant threat, particularly in high-risk patients. Although nirmatrelvir and ensitrelvir both target the viral 3CL protease (Mpro), their distinct susceptibility profiles may allow alternative therapeutic approaches. Here, we identify...
Antimicrobial resistanceAntiviral agentsAntiviralsSARS-CoV-2
10.1038/S41467-025-65767-Z
ISSN:2041-1723
Conditional diffusion with locality-aware modal alignment for generating diverse protein conformational ensembles
Baoli Wang•Chenglin Wang•Jingyang Chen•Danlin Liu•Changzhi Sun等 8 人
Nature Machine Intelligence
2026
•2026/2/25
•Vol.8 No.3 p.415-434
Recent advances in artificial intelligence have enabled accurate prediction of a protein’s stable structure solely based on its amino acid sequence. However, capturing the complete conformational landscape of a protein and its dynamic flexibility remains challenging. Here we developed modal-aligned ...
Computational modelsProtein structure predictions
10.1038/S42256-026-01198-9
ISSN:2522-5839
A eukaryotic-like ubiquitination system in bacterial antiviral defence
Lydia R. Chambers•Qiaozhen Ye•Jiaxi Cai•Minheng Gong•Hannah E. Ledvina等 9 人
Nature
2024
•2024/7/17
•Vol.631 No.8022 p.843-849
Ubiquitination pathways have crucial roles in protein homeostasis, signalling and innate immunity1–3. In these pathways, an enzymatic cascade of E1, E2 and E3 proteins conjugates ubiquitin or a ubiquitin-like protein (Ubl) to target-protein lysine residues4. Bacteria encode ancient relatives of E1 a...
BacteriophagesBiochemistryX-ray crystallography
10.1038/S41586-024-07730-4
ISSN:0028-0836
Rational design of 19F NMR labelling sites to probe protein structure and interactions
Julian O. Streit•Sammy H. S. Chan•Saifu Daya•John Christodoulou
Nature Communications
2025
•2025/5/8
•Vol.16 No.1 p.1-15
Proteins are investigated in increasingly more complex biological systems, where 19F NMR is proving highly advantageous due to its high gyromagnetic ratio and background-free spectra. Its application has, however, been hindered by limited chemical shift dispersions and an incomprehensive relationshi...
Molecular conformationMolecular modellingSolution-state NMR
10.1038/S41467-025-59105-6
ISSN:2041-1723
Amino acid insertion in Bat MHC-I enhances complex stability and augments peptide presentation
Suqiu Wang•Liangzhen Zheng•Xiaohui Wei•Zehui Qu•Liubao Du等 7 人
Communications Biology
2024
•2024/5/16
•Vol.7 No.1 p.1-14
Bats serve as reservoirs for numerous zoonotic viruses, yet they typically remain asymptomatic owing to their unique immune system. Of particular significance is the MHC-I in bats, which plays crucial role in anti-viral response and exhibits polymorphic amino acid (AA) insertions. This study demonst...
Antigen presentationMHC class I
10.1038/S42003-024-06292-5
ISSN:2399-3642
Structural insights into the Thermus thermophilus type IV pilus machinery assembling two distinct pili
Alexander Neuhaus•Mathew McLaren•Michail N. Isupov•Matthew Gaines•Emma Buzzard等 10 人
Communications Biology
2026
•2026/3/31
•Vol.9 No.1 p.4740
Type IV pili are long, filamentous structures that extend from bacterial cell surfaces, enabling cells to respond to changing environments and facilitating genome plasticity. Thermus thermophilus HB27 produces two different type IV pili, each exhibiting distinct structural and functional properties....
Cryoelectron microscopyCryoelectron tomographyProtein structure predictions
10.1038/S42003-026-09762-0
ISSN:2399-3642
Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm
Hongwu Qian•Pingping Cao•Miaohui Hu•Shuai Gao•Nieng Yan等 6 人
Nature Communications
2019
•2019/5/24
•Vol.10 No.1 p.1-9
The Hedgehog (Hh) pathway controls embryonic development and postnatal tissue maintenance and regeneration. Inhibition of Hh receptor Patched (Ptch) by the Hh ligands relieves suppression of signaling cascades. Here, we report the cryo-EM structure of tetrameric Ptch1 in complex with the palmitoylat...
Cryoelectron microscopyMembrane proteins
10.1038/S41467-019-10234-9
ISSN:2041-1723
Cryo-EM structure of human Wntless in complex with Wnt3a
Zhong Qing•Zhao Yanyu•Ye Fangfei•Xiao Zaiyu•Huang Gaoxingyu等 18 人
Nature Communications
2021
•2021/7/27
•Vol.12 No.1 p.1-8
Wntless (WLS), an evolutionarily conserved multi-pass transmembrane protein, is essential for secretion of Wnt proteins. Wnt-triggered signaling pathways control many crucial life events, whereas aberrant Wnt signaling is tightly associated with many human diseases including cancers. Here, we report...
Cell signallingCryoelectron microscopy
10.1038/S41467-021-24731-3
ISSN:2041-1723
Epitope-anchored contrastive transfer learning for paired CD8+ T cell receptor–antigen recognition
Yumeng Zhang•Zhikang Wang•Yunzhe Jiang•Dene R. Littler•Mark Gerstein等 9 人
Nature Machine Intelligence
2024
•2024/10/22
•00 p.1-15
Understanding the mechanisms of T cell antigen recognition that underpin adaptive immune responses is critical for developing vaccines, immunotherapies and treatments against autoimmune diseases. Despite extensive research efforts, accurate prediction of T cell receptor (TCR)–antigen binding pairs r...
Machine learningProtein function predictionsSARS-CoV-2
10.1038/S42256-024-00913-8
ISSN:2522-5839
Seasonal antigenic prediction of influenza A H3N2 using machine learning
Syed Awais W. Shah•Daniel P. Palomar•Ian Barr•Leo L. M. Poon•Ahmed Abdul Quadeer等 6 人
Nature Communications
2024
•2024/5/7
•Vol.15 No.1 p.1-12
Antigenic characterization of circulating influenza A virus (IAV) isolates is routinely assessed by using the hemagglutination inhibition (HI) assays for surveillance purposes. It is also used to determine the need for annual influenza vaccine updates as well as for pandemic preparedness. Performing...
Computational modelsInfluenza virusMachine learningPolicy and public health in microbiologyViral evolution
10.1038/S41467-024-47862-9
ISSN:2041-1723
Time-resolved β-lactam cleavage by L1 metallo-β-lactamase
Wilamowski M.•Sherrell D. A.•Kim Y.•Lavens A.•Henning R. W.等 13 人
Nature Communications
2022
•2022/11/30
•Vol.13 No.1 p.1-12
Serial x-ray crystallography can uncover binding events, and subsequent chemical conversions occurring during enzymatic reaction. Here, we reveal the structure, binding and cleavage of moxalactam antibiotic bound to L1 metallo-β-lactamase (MBL) from Stenotrophomonas maltophilia. Using time-resolved ...
Molecular biologyX-ray crystallography
10.1038/S41467-022-35029-3
ISSN:2041-1723
Cryo-EM structure of a lysozyme-derived amyloid fibril from hereditary amyloidosis
Sara Karimi-Farsijani•Kartikay Sharma•Marijana Ugrina•Lukas Kuhn•Peter Benedikt Pfeiffer等 12 人
Nature Communications
2024
•2024/11/7
•Vol.15 No.1 p.1-9
Systemic ALys amyloidosis is a debilitating protein misfolding disease that arises from the formation of amyloid fibrils from C-type lysozyme. We here present a 2.8 Å cryo-electron microscopy structure of an amyloid fibril, which was isolated from the abdominal fat tissue of a patient who expressed ...
Cryoelectron microscopyProtein aggregation
10.1038/S41467-024-54091-7
ISSN:2041-1723
Dynamic spatiotemporal determinants modulate GPCR:G protein coupling selectivity and promiscuity
Sandhu Manbir•Cho Aaron•Ma Ning•Mukhaleva Elizaveta•Namkung Yoon等 12 人
Nature Communications
2022
•2022/12/2
•Vol.13 No.1 p.1-14
Recent studies have shown that G protein coupled receptors (GPCRs) show selective and promiscuous coupling to different Gα protein subfamilies and yet the mechanisms of the range of coupling preferences remain unclear. Here, we use Molecular Dynamics (MD) simulations on ten GPCR:G protein complexes ...
BiophysicsComputational biology and bioinformaticsG protein-coupled receptorsProtein function predictions
10.1038/S41467-022-34055-5
ISSN:2041-1723
Synovial sarcoma X breakpoint 1 protein uses a cryptic groove to selectively recognize H2AK119Ub nucleosomes
Zebin Tong•Huasong Ai•Ziyu Xu•Kezhang He•Guo-Chao Chu等 14 人
Nature Structural & Molecular Biology
2024
•2024/1/4
•00 p.1-11
The cancer-specific fusion oncoprotein SS18–SSX1 disturbs chromatin accessibility by hijacking the BAF complex from the promoters and enhancers to the Polycomb-repressed chromatin regions. This process relies on the selective recognition of H2AK119Ub nucleosomes by synovial sarcoma X breakpoint 1 (S...
ChromatinCryoelectron microscopyHistone post-translational modificationsUbiquitylation
10.1038/S41594-023-01141-1
ISSN:1545-9993
A natural biogenic nanozyme for scavenging superoxide radicals
Long Ma•Jia-Jia Zheng•Ning Zhou•Ruofei Zhang•Long Fang等 10 人
Nature Communications
2024
•2024/1/3
•Vol.15 No.1 p.1-17
Biominerals, the inorganic minerals of organisms, are known mainly for their physical property-related functions in modern living organisms. Our recent discovery of the enzyme-like activities of nanomaterials, coined as nanozyme, inspires the hypothesis that nano-biominerals might function as enzyme...
BiocatalysisBiomineralizationMetalloproteins
10.1038/S41467-023-44463-W
ISSN:2041-1723
C-Glycoside metabolism in the gut and in nature: Identification, characterization, structural analyses and distribution of C-C bond-cleaving enzymes
Mori Takahiro•Kumano Takuto•He Haibing•Watanabe Satomi•Senda Miki等 15 人
Nature Communications
2021
•2021/11/2
•Vol.12 No.1 p.1-12
C-Glycosides, in which a sugar moiety is linked via a carbon-carbon (C-C) bond to a non-sugar moiety (aglycone), are found in our food and medicine. The C-C bond is cleaved by intestinal microbes and the resulting aglycones exert various bioactivities. Although the enzymes responsible for the reacti...
Bacterial structural biologyEnzyme mechanismsX-ray crystallography
10.1038/S41467-021-26585-1
ISSN:2041-1723
RPEL-family rhoGAPs link Rac/Cdc42 GTP loading to G-actin availability
Jessica Diring•Stephane Mouilleron•Neil Q. McDonald•Richard Treisman
Nature Cell Biology
2019
•2019/6/17
•Vol.21 No.7 p.845-855
RPEL proteins, which contain the G-actin-binding RPEL motif, coordinate cytoskeletal processes with actin dynamics. We show that the ArhGAP12- and ArhGAP32-family GTPase-activating proteins (GAPs) are RPEL proteins. We determine the structure of the ArhGAP12/G-actin complex, and show that G-actin co...
ActinRHO signalling
10.1038/S41556-019-0337-Y
ISSN:1465-7392
LYCHOS is a human hybrid of a plant-like PIN transporter and a GPCR
Charles Bayly-Jones•Christopher J. Lupton•Alastair C. Keen•Shuqi Dong•Chantel Mastos等 13 人
Nature
2024
•2024/10/2
•00 p.1-7
Lysosomes have crucial roles in regulating eukaryotic metabolism and cell growth by acting as signalling platforms to sense and respond to changes in nutrient and energy availability1. LYCHOS (GPR155) is a lysosomal transmembrane protein that functions as a cholesterol sensor, facilitating the chole...
Cell growthCryoelectron microscopy
10.1038/S41586-024-08012-9
ISSN:0028-0836
Structural deficits in key domains of Shank2 lead to alterations in postsynaptic nanoclusters and to a neurodevelopmental disorder in humans
Hassani Nia Fatemeh•Woike Daniel•Bento Isabel•Niebling Stephan•Tibbe Debora等 19 人
Molecular Psychiatry
2022
•2022/11/30
•00 p.1-15
Postsynaptic scaffold proteins such as Shank, PSD-95, Homer and SAPAP/GKAP family members establish the postsynaptic density of glutamatergic synapses through a dense network of molecular interactions. Mutations in SHANK genes are associated with neurodevelopmental disorders including autism and int...
Autism spectrum disordersCell biology
10.1038/S41380-022-01882-3
ISSN:1359-4184
Shigella infection is facilitated by interaction of human enteric α-defensin 5 with colonic epithelial receptor P2Y11
Dan Xu•Mengyao Guo•Xin Xu•Gan Luo•Yaxin Liu等 21 人
Nature Microbiology
2025
•2025/2/3
•Vol.10 No.2 p.509-526
Human enteric α-defensin 5 (HD5) is an immune system peptide that acts as an important antimicrobial factor but is also known to promote pathogen infections by enhancing adhesion of the pathogens. The mechanistic basis of these conflicting functions is unknown. Here we show that HD5 induces abundant...
Cellular microbiologyInfectionPathogens
10.1038/S41564-024-01901-9
ISSN:2058-5276
Dirigent gene editing of gossypol enantiomers for toxicity-depleted cotton seeds
Lin Jia-Ling•Fang Xin•Li Jian-Xu•Chen Zhi-Wen•Wu Wen-Kai等 14 人
Nature Plants
2023
•2023/3/16
•00 p.1-11
Axial chirality of biaryls can generate varied bioactivities. Gossypol is a binaphthyl compound made by cotton plants. Of its two axially chiral isomers, (−)-gossypol is the bioactive form in mammals and has antispermatogenic activity, and its accumulation in cotton seeds poses health concerns. Here...
Plant evolutionSecondary metabolismTransgenic plants
10.1038/S41477-023-01376-2
ISSN:2055-0278
Cryo-EM structures of CRAF/MEK1/14-3-3 complexes in autoinhibited and open-monomer states reveal features of RAF regulation
Dong Man Jang•Kayla Boxer•Byung Hak Ha•Emre Tkacik•Talya Levitz等 10 人
Nature Communications
2025
•2025/9/1
•Vol.16 No.1 p.1-14
CRAF (RAF1) is one of three RAF-family kinases that initiate MAP kinase signaling in response to activated RAS and is essential for oncogenic signaling from mutant KRAS. Like BRAF, CRAF is regulated by 14-3-3 engagement and by intramolecular autoinhibitory interactions of its N-terminal regulatory r...
CancerCryoelectron microscopyKinasesPhosphoproteinsPhosphorylation
10.1038/S41467-025-63227-2
ISSN:2041-1723
A cell-free nanobody engineering platform rapidly generates SARS-CoV-2 neutralizing nanobodies
Chen Xun•Gentili Matteo•Hacohen Nir•Regev Aviv
Nature Communications
2021
•2021/9/17
•Vol.12 No.1 p.1-14
Antibody engineering technologies face increasing demands for speed, reliability and scale. We develop CeVICA, a cell-free nanobody engineering platform that uses ribosome display for in vitro selection of nanobodies from a library of 1011 randomized sequences. We apply CeVICA to engineer nanobodies...
Antibody fragment therapyAntibody generationProtein design
10.1038/S41467-021-25777-Z
ISSN:2041-1723
Deciphering the molecular basis of lipoprotein recognition and transport by LolCDE
Wen Qiao•Chongrong Shen•Yujiao Chen•Shenghai Chang•Xin Wang等 16 人
Signal Transduction And Targeted Therapy
2024
•2024/12/27
•Vol.9 No.1 p.1-12
Outer membrane (OM) lipoproteins serve vital roles in Gram-negative bacteria, contributing to their pathogenicity and drug resistance. For these lipoproteins to function, they must be transported from the inner membrane (IM), where they are assembled, to the OM by the ABC transporter LolCDE. We have...
MicrobiologyStructural biology
10.1038/S41392-024-02067-W
ISSN:2059-3635
The 3D mutational constraint on amino acid sites in the human proteome
Li Bian•Roden Dan M.•Capra John A.
Nature Communications
2022
•2022/6/7
•Vol.13 No.1 p.1-15
Quantification of the tolerance of protein sites to genetic variation has become a cornerstone of variant interpretation. We hypothesize that the constraint on missense variation at individual amino acid sites is largely shaped by direct interactions with 3D neighboring sites. To quantify this const...
BiophysicsComputational biology and bioinformaticsGenetics
10.1038/S41467-022-30936-X
ISSN:2041-1723
Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs
Rajagopal Murugan•Stephen W. Scally•Giulia Costa•Ghulam Mustafa•Elaine Thai等 11 人
Nature Medicine
2020
•2020/5/25
•Vol.26 No.7 p.1135-1145
The circumsporozoite protein of the human malaria parasite Plasmodium falciparum (PfCSP) is the main target of antibodies that prevent the infection and disease, as shown in animal models. However, the limited efficacy of the PfCSP-based vaccine RTS,S calls for a better understanding of the mechanis...
Adaptive immunityApplied immunologyImmunologyMalariaVaccines
10.1038/S41591-020-0881-9
ISSN:1078-8956
Ubiquitous purine sensor modulates diverse signal transduction pathways in bacteria
Elizabet Monteagudo-Cascales•Vadim M. Gumerov•Matilde Fernández•Miguel A. Matilla•José A. Gavira等 7 人
Nature Communications
2024
•2024/7/12
•Vol.15 No.1 p.1-13
Purines and their derivatives control intracellular energy homeostasis and nucleotide synthesis, and act as signaling molecules. Here, we combine structural and sequence information to define a purine-binding motif that is present in sensor domains of thousands of bacterial receptors that modulate m...
BacteriaBacterial structural biologyCell signalling
10.1038/S41467-024-50275-3
ISSN:2041-1723
Structure of a Ty1 restriction factor reveals the molecular basis of transposition copy number control
Cottee Matthew A.•Beckwith Sean L.•Letham Suzanne C.•Kim Sarah J.•Young George R.等 8 人
Nature Communications
2021
•2021/9/22
•Vol.12 No.1 p.1-17
Excessive replication of Saccharomyces cerevisiae Ty1 retrotransposons is regulated by Copy Number Control, a process requiring the p22/p18 protein produced from a sub-genomic transcript initiated within Ty1 GAG. In retrotransposition, Gag performs the capsid functions required for replication and r...
TranspositionX-ray crystallography
10.1038/S41467-021-25849-0
ISSN:2041-1723
PTRAMP, CSS and Ripr form a conserved complex required for merozoite invasion of Plasmodium species into erythrocytes
Benjamin A. Seager•Pailene S. Lim•Xiao Xiao•Keng Heng Lai•Lionel Brice Feufack-Donfack等 19 人
Nature Communications
2026
•2026/1/26
•Vol.17 No.1 p.17800
Invasion of erythrocytes by members of the Plasmodium genus is an essential step of the parasite lifecycle, orchestrated by numerous host-parasite interactions. In P. falciparum Rh5, with PfCyRPA, PfRipr, PfCSS, and PfPTRAMP, forms the essential PCRCR complex which binds basigin on the erythrocyte s...
Genetics researchParasite biologyX-ray crystallography
10.1038/S41467-026-68486-1
ISSN:2041-1723
Cryo-EM structures of Escherichia coli Ec86 retron complexes reveal architecture and defence mechanism
Wang Yanjing•Guan Zeyuan•Wang Chen•Nie Yangfan•Chen Yibei等 17 人
Nature Microbiology
2022
•2022/8/18
•Vol.7 No.9 p.1480-1489
First discovered in the 1980s, retrons are bacterial genetic elements consisting of a reverse transcriptase and a non-coding RNA (ncRNA). Retrons mediate antiphage defence in bacteria but their structure and defence mechanisms are unknown. Here, we investigate the Escherichia coli Ec86 retron and us...
Cryoelectron microscopyPhage biology
10.1038/S41564-022-01197-7
ISSN:2058-5276
Structure and function of the geldanamycin amide synthase from Streptomyces hygroscopicus
Wiebke Ewert•Christian Bartens•Jekaterina Ongouta•Monika Holmes•Anja Heutling等 10 人
Nature Communications
2025
•2025/3/12
•Vol.16 No.1 p.1-13
Amide synthases catalyze the formation of macrolactam rings from aniline-containing polyketide-derived seco-acids as found in the important class of ansamycin antibiotics. One of these amide synthases is the geldanamycin amide synthase GdmF, which we recombinantly expressed, purified and studied in ...
Enzyme mechanismsEnzymesNatural product synthesisX-ray crystallography
10.1038/S41467-025-57013-3
ISSN:2041-1723
PARP1-HPF1 structure and dynamics on nicked DNA suggest a mechanism for acute and localized ADP-ribosylation
Aleksandr Sverzhinsky•Huijun Xue•Marie-France Langelier•Marcelo V. Muniz Corrêa•Joshua Del Mundo等 9 人
Nature Communications
2026
•2026/2/16
•Vol.17 No.1 p.28250
PARP1 detection of DNA strand breaks allosterically leads to PARP1 synthesis of poly(ADP-ribose) modifications that signal DNA damage. HPF1 engages activated PARP1 to control modification site selection. Understanding of the mechanism of DNA break detection and catalytic activation is incomplete, du...
Cryoelectron microscopySAXSSingle-molecule biophysics
10.1038/S41467-026-69375-3
ISSN:2041-1723
Binding of regulatory proteins to nucleosomes is modulated by dynamic histone tails
Peng Yunhui•Li Shuxiang•Onufriev Alexey•Landsman David•Panchenko Anna R.
Nature Communications
2021
•2021/9/6
•Vol.12 No.1 p.1-12
Little is known about the roles of histone tails in modulating nucleosomal DNA accessibility and its recognition by other macromolecules. Here we generate extensive atomic level conformational ensembles of histone tails in the context of the full nucleosome, totaling 65 microseconds of molecular dyn...
Computational biophysicsComputational modelsIntrinsically disordered proteinsMolecular modelling
10.1038/S41467-021-25568-6
ISSN:2041-1723
Structural asymmetry governs the assembly and GTPase activity of McrBC restriction complexes
Yiming Niu•Hiroshi Suzuki•Christopher J. Hosford•Thomas Walz•Joshua S. Chappie
Nature Communications
2020
•2020/11/20
•Vol.11 No.1 p.1-17
McrBC complexes are motor-driven nucleases functioning in bacterial self-defense by cleaving foreign DNA. The GTP-specific AAA + protein McrB powers translocation along DNA and its hydrolysis activity is stimulated by its partner nuclease McrC. Here, we report cryo-EM structures of Thermococcus gamm...
Cryoelectron microscopyDNA-binding proteinsDNA restriction-modification enzymesGTP-binding protein regulatorsHydrolases
10.1038/S41467-020-19735-4
ISSN:2041-1723
Defining ortholog-specific UHRF1 inhibition by STELLA for cancer therapy
Wenjing Bai•Jinxin Xu•Wenbin Gu•Danyang Wang•Ying Cui等 22 人
Nature Communications
2025
•2025/1/8
•Vol.16 No.1 p.1-22
UHRF1 maintains DNA methylation by recruiting DNA methyltransferases to chromatin. In mouse, these dynamics are potently antagonized by a natural UHRF1 inhibitory protein STELLA, while the comparable effects of its human ortholog are insufficiently characterized, especially in cancer cells. Herein, ...
Cancer genomicsCancer preventionTargeted therapies
10.1038/S41467-024-55481-7
ISSN:2041-1723
Mechanistic insights into lanthipeptide modification by a distinct subclass of LanKC enzyme that forms dimers
Yifan Li•Kai Shao•Zhaoxing Li•Kongfu Zhu•Bee Koon Gan等 8 人
Nature Communications
2024
•2024/8/17
•Vol.15 No.1 p.1-20
Naturally occurring lanthipeptides, peptides post-translationally modified by various enzymes, hold significant promise as antibiotics. Despite extensive biochemical and structural studies, the events preceding peptide modification remain poorly understood. Here, we identify a distinct subclass of l...
Cryoelectron microscopyEnzymesMass spectrometry
10.1038/S41467-024-51600-6
ISSN:2041-1723
Exploring the structural landscape of DNA maintenance proteins
Kenneth Bødkter Schou•Samuel Mandacaru•Muhammad Tahir•Nikola Tom•Ann-Sofie Nilsson等 9 人
Nature Communications
2024
•2024/9/5
•Vol.15 No.1 p.1-17
Evolutionary annotation of genome maintenance (GM) proteins has conventionally been established by remote relationships within protein sequence databases. However, often no significant relationship can be established. Highly sensitive approaches to attain remote homologies based on iterative profile...
Protein sequence analysesStructural biology
10.1038/S41467-024-49983-7
ISSN:2041-1723
Structural insights into the gating mechanism of the fission yeast phosphate exporter SpXpr1
Hui Yang•Yuechan Wang•Chenxi Yue•Xinran Li•Yifei Wang等 7 人
Cell Discovery
2026
•2026/4/15
•Vol.12 No.1 p.270
Phosphate homeostasis is essential for fundamental cellular processes, including energy metabolism, signal transduction, and nucleic acid synthesis. Although XPR1 family proteins are conserved phosphate exporters throughout eukaryotes, their structural mechanisms in organisms other than mammals and ...
Electron microscopyProtein transport
10.1038/S41421-026-00883-8
ISSN:2056-5968
The Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation
Christopher B. Nelson•Samuel Rogers•Kaushik Roychoudhury•Yaw Sing Tan•Caroline J. Atkinson等 15 人
Nature Communications
2024
•2024/2/15
•Vol.15 No.1 p.1-17
The Eyes Absent proteins (EYA1-4) are a biochemically unique group of tyrosine phosphatases known to be tumour-promoting across a range of cancer types. To date, the targets of EYA phosphatase activity remain largely uncharacterised. Here, we identify Polo-like kinase 1 (PLK1) as an interactor and p...
MitosisOncogenesPhosphorylation
10.1038/S41467-024-45683-4
ISSN:2041-1723
Mining the cellular inventory of pyridoxal phosphate-dependent enzymes with functionalized cofactor mimics
Annabelle Hoegl•Matthew B. Nodwell•Volker C. Kirsch•Nina C. Bach•Martin Pfanzelt等 8 人
Nature Chemistry
2018
•2018/10/8
•Vol.10 No.12 p.1234-1245
Pyridoxal phosphate (PLP) is an enzyme cofactor required for the chemical transformation of biological amines in many central cellular processes. PLP-dependent enzymes (PLP-DEs) are ubiquitous and evolutionarily diverse, making their classification based on sequence homology challenging. Here we pre...
Chemical modificationChemical toolsEnzymesProteomics
10.1038/S41557-018-0144-2
ISSN:1755-4330
Somatic mutation distribution across tumour cohorts provides a signal for positive selection in cancer
Boström Martin•Larsson Erik
Nature Communications
2022
•2022/11/17
•Vol.13 No.1 p.1-9
Cancer gene discovery is reliant on distinguishing driver mutations from a multitude of passenger mutations in tumour genomes. While driver genes may be revealed based on excess mutation recurrence or clustering, there is a need for orthogonal principles. Here, we take advantage of the fact that non...
CancerCancer genomicsComputational biology and bioinformaticsGenome evolutionMutation
10.1038/S41467-022-34746-Z
ISSN:2041-1723
The β-subunit of tryptophan synthase is a latent tyrosine synthase
Patrick J. Almhjell•Kadina E. Johnston•Nicholas J. Porter•Jennifer L. Kennemur•Vignesh C. Bhethanabotla等 7 人
Nature Chemical Biology
2024
•2024/5/14
•00 p.1-8
Aromatic amino acids and their derivatives are diverse primary and secondary metabolites with critical roles in protein synthesis, cell structure and integrity, defense and signaling. All de novo aromatic amino acid production relies on a set of ancient and highly conserved chemistries. Here we intr...
BiocatalysisEnzyme mechanismsEnzymes
10.1038/S41589-024-01619-Z
ISSN:1552-4450
The small CRL4CSA ubiquitin ligase component DDA1 regulates transcription-coupled repair dynamics
Diana A. Llerena Schiffmacher•Shun-Hsiao Lee•Katarzyna W. Kliza•Arjan F. Theil•Masaki Akita等 20 人
Nature Communications
2024
•2024/7/29
•Vol.15 No.1 p.1-17
Transcription-blocking DNA lesions are specifically targeted by transcription-coupled nucleotide excision repair (TC-NER), which removes a broad spectrum of DNA lesions to preserve transcriptional output and thereby cellular homeostasis to counteract aging. TC-NER is initiated by the stalling of RNA...
DNA damage responseNucleotide excision repair
10.1038/S41467-024-50584-7
ISSN:2041-1723
Delineating the stepwise millisecond allosteric activation mechanism of the class C GPCR dimer mGlu5
Mingyu Li•Xiaobing Lan•Xinchao Shi•Chunhao Zhu•Xun Lu等 8 人
Nature Communications
2024
•2024/8/30
•Vol.15 No.1 p.1-14
Two-thirds of signaling hormones and one-third of approved drugs exert their effects by binding and modulating the G protein-coupled receptors (GPCRs) activation. While the activation mechanism for monomeric GPCRs has been well-established, little is known about GPCRs in dimeric form. Here, by combi...
Computational biophysicsG protein-coupled receptorsProtein function predictions
10.1038/S41467-024-51999-Y
ISSN:2041-1723
Heme and hemoglobin utilization by Mycobacterium tuberculosis
Avishek Mitra•Ying-Hui Ko•Gino Cingolani•Michael Niederweis
Nature Communications
2019
•2019/9/18
•Vol.10 No.1 p.1-14
Iron is essential for growth of Mycobacterium tuberculosis (Mtb), but most iron in the human body is stored in heme within hemoglobin. Here, we demonstrate that the substrate-binding protein DppA of the inner membrane Dpp transporter is required for heme and hemoglobin utilization by Mtb. The 1.27 Å...
Bacterial structural biologyMetalloproteinsPathogens
10.1038/S41467-019-12109-5
ISSN:2041-1723
Structural basis of CAX1 autoinhibition by its amino-terminal domain in Arabidopsis thaliana
Kun Wang•Chunhui Ma•Guanglin Chen•Zhisen Yang•Yongxiang Gao等 8 人
Nature Plants
2025
•2025/9/2
•00 p.1-12
Calcium homeostasis is tightly regulated due to the essential roles of calcium ions (Ca2+) in various cellular processes. CAX1 in Arabidopsis thaliana (AtCAX1) serves as a Ca2+/H+ exchanger transporting excess cytosolic Ca2+ into the vacuole, which is modulated by kinase phosphorylation in response ...
Cryoelectron microscopyPlant signalling
10.1038/S41477-025-02104-8
ISSN:2055-0278
Structural basis for UFM1 transfer from UBA5 to UFC1
Kumar Manoj•Padala Prasanth•Fahoum Jamal•Hassouna Fouad•Tsaban Tomer等 13 人
Nature Communications
2021
•2021/9/29
•Vol.12 No.1 p.1-13
Ufmylation is a post-translational modification essential for regulating key cellular processes. A three-enzyme cascade involving E1, E2 and E3 is required for UFM1 attachment to target proteins. How UBA5 (E1) and UFC1 (E2) cooperatively activate and transfer UFM1 is still unclear. Here, we present ...
Post-translational modificationsUbiquitinsX-ray crystallography
10.1038/S41467-021-25994-6
ISSN:2041-1723
Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2
Youngchang Kim•Jacek Wower•Natalia Maltseva•Changsoo Chang•Robert Jedrzejczak等 11 人
Communications Biology
2021
•2021/2/9
•Vol.4 No.1 p.1-11
SARS-CoV-2 Nsp15 is a uridine-specific endoribonuclease with C-terminal catalytic domain belonging to the EndoU family that is highly conserved in coronaviruses. As endoribonuclease activity seems to be responsible for the interference with the innate immune response, Nsp15 emerges as an attractive ...
Molecular biologyStructural biology
10.1038/S42003-021-01735-9
ISSN:2399-3642
FungAMR: a comprehensive database for investigating fungal mutations associated with antimicrobial resistance
Camille Bédard•Alicia Pageau•Anna Fijarczyk•David Mendoza-Salido•Alejandro J. Alcañiz等 29 人
Nature Microbiology
2025
•2025/8/11
•00 p.1-15
Antimicrobial resistance (AMR) is a global threat, especially in fungal pathogens. To optimize the use of available antifungals, we need rapid detection and monitoring tools that rely on high-quality AMR mutation data. Here we present FungAMR, a resource based on manual curation of 501 published stu...
Antifungal agentsFungal genomics
10.1038/S41564-025-02084-7
ISSN:2058-5276
Mapping specificity, cleavage entropy, allosteric changes and substrates of blood proteases in a high-throughput screen
Federico Uliana•Matej Vizovišek•Laura Acquasaliente•Rodolfo Ciuffa•Andrea Fossati等 12 人
Nature Communications
2021
•2021/3/16
•Vol.12 No.1 p.1-18
Proteases are among the largest protein families and critical regulators of biochemical processes like apoptosis and blood coagulation. Knowledge of proteases has been expanded by the development of proteomic approaches, however, technology for multiplexed screening of proteases within native enviro...
High-throughput screeningProteasesProteolysisProteomics
10.1038/S41467-021-21754-8
ISSN:2041-1723
DutaFabs are engineered therapeutic Fab fragments that can bind two targets simultaneously
Roland Beckmann•Kristian Jensen•Sebastian Fenn•Janina Speck•Katrin Krause等 12 人
Nature Communications
2021
•2021/1/29
•Vol.12 No.1 p.1-13
We report the development of a platform of dual targeting Fab (DutaFab) molecules, which comprise two spatially separated and independent binding sites within the human antibody CDR loops: the so-called H-side paratope encompassing HCDR1, HCDR3 and LCDR2, and the L-side paratope encompassing LCDR1, ...
Antibody fragment therapyMacular degenerationX-ray crystallography
10.1038/S41467-021-20949-3
ISSN:2041-1723
Cryo-EM structure of Helicobacter pylori urease with an inhibitor in the active site at 2.0 Å resolution
Eva S. Cunha•Xiaorui Chen•Marta Sanz-Gaitero•Deryck J. Mills•Hartmut Luecke
Nature Communications
2021
•2021/1/11
•Vol.12 No.1 p.1-8
Infection of the human stomach by Helicobacter pylori remains a worldwide problem and greatly contributes to peptic ulcer disease and gastric cancer. Without active intervention approximately 50% of the world population will continue to be infected with this gastric pathogen. Current eradication, ca...
Cryoelectron microscopyDrug discoveryHydrolasesPathogens
10.1038/S41467-020-20485-6
ISSN:2041-1723
Pan-sarbecovirus prophylaxis with human anti-ACE2 monoclonal antibodies
Fengwen Zhang•Jesse Jenkins•Renan V. H. de Carvalho•Sandra Nakandakari-Higa•Teresia Chen等 17 人
Nature Microbiology
2023
•2023/5/15
•00 p.1-13
Human monoclonal antibodies (mAbs) that target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been isolated from convalescent individuals and developed into therapeutics for SARS-CoV-2 infection. However, therapeutic mAbs for SARS-CoV-2 have been rendered obsolet...
SARS-CoV-2Viral infection
10.1038/S41564-023-01389-9
ISSN:2058-5276
Pharmacophore-oriented 3D molecular generation toward efficient feature-customized drug discovery
Jian Peng•Jun-Lin Yu•Zeng-Bao Yang•Yi-Ting Chen•Si-Qi Wei等 9 人
Nature Computational Science
2025
•2025/8/26
•00 p.1-17
Molecular generation is a cutting-edge technology with the potential to revolutionize intelligent drug discovery. However, currently reported ligand-based or structure-based molecular generation methods remain unpractical for real-world drug discovery. Here we propose an explicit pharmacophore-orien...
Computational scienceDrug discoveryMedicinal chemistry
10.1038/S43588-025-00850-5
ISSN:2662-8457
Clustering-predicted structures at the scale of the known protein universe
Inigo Barrio-Hernandez•Jingi Yeo•Jürgen Jänes•Milot Mirdita•Cameron L. M. Gilchrist等 10 人
Nature
2023
•2023/9/13
•00 p.1-9
Proteins are key to all cellular processes and their structure is important in understanding their function and evolution. Sequence-based predictions of protein structures have increased in accuracy1, and over 214 million predicted structures are available in the AlphaFold database2. However, studyi...
Protein analysisSoftwareStructural biology
10.1038/S41586-023-06510-W
ISSN:0028-0836
High-resolution characterization of gene function using single-cell CRISPR tiling screen
Lu Yang•Anthony K. N. Chan•Kazuya Miyashita•Christopher D. Delaney•Xi Wang等 26 人
Nature Communications
2021
•2021/7/1
•Vol.12 No.1 p.1-9
Identification of novel functional domains and characterization of detailed regulatory mechanisms in cancer-driving genes is critical for advanced cancer therapy. To date, CRISPR gene editing has primarily been applied to defining the role of individual genes. Recently, high-density mutagenesis via ...
Cancer geneticsCRISPR-Cas systemsEpigeneticsHigh-throughput screening
10.1038/S41467-021-24324-0
ISSN:2041-1723
Discovering small-molecule senolytics with deep neural networks
Wong Felix•Omori Satotaka•Donghia Nina M.•Zheng Erica J.•Collins James J.
Nature Aging
2023
•2023/5/4
•00 p.1-17
The accumulation of senescent cells is associated with aging, inflammation and cellular dysfunction. Senolytic drugs can alleviate age-related comorbidities by selectively killing senescent cells. Here we screened 2,352 compounds for senolytic activity in a model of etoposide-induced senescence and ...
AgeingComputer modellingDrug discoveryMachine learningSenescence
10.1038/S43587-023-00415-Z
ISSN:2662-8465
Mechanism of substrate transport and inhibition of the human LAT1-4F2hc amino acid transporter
Renhong Yan•Yaning Li•Jennifer Müller•Yuanyuan Zhang•Simon Singer等 10 人
Cell Discovery
2021
•2021/3/23
•Vol.7 No.1 p.1-8
LAT1 (SLC7A5) is one of the representative light chain proteins of heteromeric amino acid transporters, forming a heterodimer with its heavy chain partner 4F2hc (SLC3A2). LAT1 is overexpressed in many types of tumors and mediates the transfer of drugs and hormones across the blood-brain barrier. Thu...
Cryoelectron microscopyMechanisms of disease
10.1038/S41421-021-00247-4
ISSN:2056-5968
Biallelic mutations in cancer genomes reveal local mutational determinants
Demeulemeester Jonas•Dentro Stefan C.•Gerstung Moritz•Van Loo Peter
Nature Genetics
2022
•2022/2/10
•Vol.54 No.2 p.128-133
The infinite sites model of molecular evolution posits that every position in the genome is mutated at most once1. By restricting the number of possible mutation histories, haplotypes and alleles, it forms a cornerstone of tumor phylogenetic analysis2 and is often implied when calling, phasing and i...
CancerComputational biology and bioinformaticsGenomics
10.1038/S41588-021-01005-8
ISSN:1061-4036
Crystal structure of SARS-CoV-2 nsp10/nsp16 2′-O-methylase and its implication on antiviral drug design
Sheng Lin•Hua Chen•Fei Ye•Zimin Chen•Fanli Yang等 10 人
Signal Transduction And Targeted Therapy
2020
•2020/7/29
•Vol.5 No.1 p.1-4
MicrobiologyStructural biology
10.1038/S41392-020-00241-4
ISSN:2059-3635
Direct stimulation of de novo nucleotide synthesis by O-GlcNAcylation
Lulu Chen•Qi Zhou•Pingfeng Zhang•Wei Tan•Yingge Li等 11 人
Nature Chemical Biology
2023
•2023/6/12
•00 p.1-11
O-linked β-N-acetyl glucosamine (O-GlcNAc) is at the crossroads of cellular metabolism, including glucose and glutamine; its dysregulation leads to molecular and pathological alterations that cause diseases. Here we report that O-GlcNAc directly regulates de novo nucleotide synthesis and nicotinamid...
Cancer therapyDNA metabolismEnzyme mechanismsGlycobiologyPost-translational modifications
10.1038/S41589-023-01354-X
ISSN:1552-4450
Activation mechanism of the class D fungal GPCR dimer Ste2
Velazhahan Vaithish•Ma Ning•Vaidehi Nagarajan•Tate Christopher G.
Nature
2022
•2022/3/16
•00 p.1-6
The fungal class D1 G-protein-coupled receptor (GPCR) Ste2 has a different arrangement of transmembrane helices compared with mammalian GPCRs and a distinct mode of coupling to the heterotrimeric G protein Gpa1–Ste2–Ste181. In addition, Ste2 lacks conserved sequence motifs such as DRY, PIF and NPXXY...
Cryoelectron microscopyG protein-coupled receptors
10.1038/S41586-022-04498-3
ISSN:0028-0836
Mycoplasma genitalium adhesin P110 binds sialic-acid human receptors
David Aparicio•Sergi Torres-Puig•Mercè Ratera•Enrique Querol•Jaume Piñol等 7 人
Nature Communications
2018
•2018/10/26
•Vol.9 No.1 p.1-11
Adhesion of pathogenic bacteria to target cells is a prerequisite for colonization and further infection. The main adhesins of the emerging sexually transmitted pathogen Mycoplasma genitalium, P140 and P110, interact to form a Nap complex anchored to the cell membrane. Herein, we present the crystal...
ImmunologyMicrobiologyX-ray crystallography
10.1038/S41467-018-06963-Y
ISSN:2041-1723
Structural and functional characterization of USP47 reveals a hot spot for inhibitor design
Sang Chul Shin•Jinyoung Park•Kyung Hee Kim•Jung Min Yoon•Jinhong Cho等 10 人
Communications Biology
2023
•2023/9/22
•Vol.6 No.1 p.1-16
USP47 is widely involved in tumor development, metastasis, and other processes while performing a more regulatory role in inflammatory responses, myocardial infarction, and neuronal development. In this study, we investigate the functional and biochemical properties of USP47, whereby depleting USP47...
Enzyme mechanismsX-ray crystallography
10.1038/S42003-023-05345-5
ISSN:2399-3642
Perturbed N-glycosylation of Halobacterium salinarum archaellum filaments leads to filament bundling and compromised cell motility
Shahar Sofer•Zlata Vershinin•Leen Mashni•Ran Zalk•Anat Shahar等 7 人
Nature Communications
2024
•2024/7/11
•Vol.15 No.1 p.1-13
The swimming device of archaea—the archaellum—presents asparagine (N)-linked glycans. While N-glycosylation serves numerous roles in archaea, including enabling their survival in extreme environments, how this post-translational modification contributes to cell motility remains under-explored. Here,...
Archaeal biologyCellular microbiologyCryoelectron microscopyGlycobiology
10.1038/S41467-024-50277-1
ISSN:2041-1723
Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies
Rory Henderson•Kara Anasti•Kartik Manne•Victoria Stalls•Carrie Saunders等 26 人
Nature Communications
2024
•2024/11/3
•Vol.15 No.1 p.1-20
Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve select...
Computational biophysicsCryoelectron microscopyProtein vaccines
10.1038/S41467-024-53120-9
ISSN:2041-1723
Cryo-EM structures of light chain fibrils from abdominal fat biopsies of multiple myeloma patients
Yuxuan Yao•Shun Yao•Yamei Xu•Qinyue Zhao•Xingyu Xiong等 12 人
Nature Communications
2026
•2026/2/24
•Vol.17 No.1 p.31370
Multiple myeloma (MM) is a hematological malignancy characterized by the abnormal proliferation of plasma cells in the bone marrow and is closely associated with systemic light chain amyloidosis (AL), a disease triggered by the amyloid aggregation of antibody light chain (LC). High-resolution struct...
Cryoelectron microscopyMyelomaProtein aggregation
10.1038/S41467-026-69784-4
ISSN:2041-1723
Identification of the bacteriophage nucleus protein interaction network
Eray Enustun•Amar Deep•Yajie Gu•Katrina T. Nguyen•Vorrapon Chaikeeratisak等 10 人
Nature Structural & Molecular Biology
2023
•2023/9/4
•00 p.1-10
In the arms race between bacteria and bacteriophages (phages), some large-genome jumbo phages have evolved a protein shell that encloses their replicating genome to protect it against host immune factors. By segregating the genome from the host cytoplasm, however, the ‘phage nucleus’ introduces the ...
Cellular microbiologyMass spectrometryPhage biologyRNA-binding proteinsX-ray crystallography
10.1038/S41594-023-01094-5
ISSN:1545-9993
Cryo-EM structures of human TMEM120A and TMEM120B
Ke Meng•Yu Yue•Zhao Changjian•Lai Shirong•Su Qiang等 13 人
Cell Discovery
2021
•2021/8/31
•Vol.7 No.1 p.1-4
Cryoelectron microscopyIon channel signalling
10.1038/S41421-021-00319-5
ISSN:2056-5968
A host–guest semibiological photosynthesis system coupling artificial and natural enzymes for solar alcohol splitting
Cai Junkai•Zhao Liang•He Cheng•Li Yanan•Duan Chunying
Nature Communications
2021
•2021/8/24
•Vol.12 No.1 p.1-11
Development of a versatile, sustainable and efficient photosynthesis system that integrates intricate catalytic networks and energy modules at the same location is of considerable future value to energy transformation. In the present study, we develop a coenzyme-mediated supramolecular host-guest se...
Coordination chemistryMolecular capsulesPhotocatalysis
10.1038/S41467-021-25362-4
ISSN:2041-1723
Merizo: a rapid and accurate protein domain segmentation method using invariant point attention
Andy M. Lau•Shaun M. Kandathil•David T. Jones
Nature Communications
2023
•2023/12/19
•Vol.14 No.1 p.1-11
The AlphaFold Protein Structure Database, containing predictions for over 200 million proteins, has been met with enthusiasm over its potential in enriching structural biological research and beyond. Currently, access to the database is precluded by an urgent need for tools that allow the efficient ...
Machine learningMolecular modellingProtein structure predictions
10.1038/S41467-023-43934-4
ISSN:2041-1723
Chemoproteogenomic stratification of the missense variant cysteinome
Heta Desai•Katrina H. Andrews•Kristina V. Bergersen•Samuel Ofori•Fengchao Yu等 13 人
Nature Communications
2024
•2024/10/28
•Vol.15 No.1 p.1-24
Cancer genomes are rife with genetic variants; one key outcome of this variation is widespread gain-of-cysteine mutations. These acquired cysteines can be both driver mutations and sites targeted by precision therapies. However, despite their ubiquity, nearly all acquired cysteines remain unidentifi...
Chemical biologyProteome informaticsProteomics
10.1038/S41467-024-53520-X
ISSN:2041-1723
Structures and inhibition of the Crimean–Congo haemorrhagic fever virus polymerase
Lu Xue•Jiacheng Gui•Hainei Pan•Fan Wu•Shenghua Gao等 21 人
Nature
2026
•2026/7/22
•00 p.1-11
Crimean–Congo haemorrhagic fever virus (CCHFV) is a tick-borne virus and causes severe, often fatal, human infections. Lacking licensed vaccines or drugs, CCHFV is a World Health Organization priority pathogen requiring urgent development of medical countermeasures1,2. The CCHFV Large (L) protein fu...
Cryoelectron microscopyPathogensRNAVirology
10.1038/S41586-026-10701-6
ISSN:0028-0836
Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia
Pappalardi Melissa B.•Keenan Kathryn•Cockerill Mark•Kellner Wendy A.•Stowell Alexandra等 62 人
Nature Cancer
2021
•2021/9/27
•00 p.1-16
DNA methylation, a key epigenetic driver of transcriptional silencing, is universally dysregulated in cancer. Reversal of DNA methylation by hypomethylating agents, such as the cytidine analogs decitabine or azacytidine, has demonstrated clinical benefit in hematologic malignancies. These nucleoside...
Cancer therapyDrug discoveryHaematological cancer
10.1038/S43018-021-00249-X
ISSN:2662-1347
VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response
Thomas Thisted•F. Donelson Smith•Arnab Mukherjee•Yuliya Kleschenko•Feng Feng等 18 人
Nature Communications
2024
•2024/4/4
•Vol.15 No.1 p.1-16
VISTA, an inhibitory myeloid-T-cell checkpoint, holds promise as a target for cancer immunotherapy. However, its effective targeting has been impeded by issues such as rapid clearance and cytokine release syndrome observed with previous VISTA antibodies. Here we demonstrate that SNS-101, a newly dev...
Antibody therapyCancer microenvironmentPreclinical researchProtein–protein interaction networks
10.1038/S41467-024-47256-X
ISSN:2041-1723
Argonaute-HNH filaments triggered by invader DNA confer bacterial immunity
Anna Kanevskaya•Manju Narwal•Lidiya Lisitskaya•Andrey V. Moiseenko•Olga S. Sokolova等 8 人
Nature Communications
2025
•2025/11/28
0Argonaute proteins provide innate immunity in all domains of life through guide-dependent recognition and cleavage of invader nucleic acids. Many short prokaryotic Argonautes (pAgos) lack nuclease activity and are instead co-encoded with tentative nuclease effectors, but their activation mechanisms ...
Bacterial structural biologyBacteriophagesEnzymesRNAi
10.1038/S41467-025-66189-7
ISSN:2041-1723
Molecular basis of host recognition of human coronavirus 229E
Yu-Xi Tsai•Yu-Chun Chien•Min-Feng Hsu•Kay-Hooi Khoo•Shang-Te Danny Hsu
Nature Communications
2025
•2025/2/27
•Vol.16 No.1 p.1-15
Human coronavirus 229E (HCoV-229E) is the earliest CoV found to infect humans. It binds to the human aminopeptidase N (hAPN) through the receptor binding domain (RBD) of its spike (S) protein to achieve host recognition. We present the cryo-electron microscopy structure of two HCoV-229E S protein in...
Cryoelectron microscopyMass spectrometryMolecular modellingVirus–host interactions
10.1038/S41467-025-57359-8
ISSN:2041-1723
Cryo-EM structure of a RAS/RAF recruitment complex
Eunyoung Park•Shaun Rawson•Anna Schmoker•Byeong-Won Kim•Sehee Oh等 8 人
Nature Communications
2023
•2023/7/29
•Vol.14 No.1 p.1-11
RAF-family kinases are activated by recruitment to the plasma membrane by GTP-bound RAS, whereupon they initiate signaling through the MAP kinase cascade. Prior structural studies of KRAS with RAF have focused on the isolated RAS-binding and cysteine-rich domains of RAF (RBD and CRD, respectively), ...
Cryoelectron microscopyKinasesOncogenes
10.1038/S41467-023-40299-6
ISSN:2041-1723
Regulation of RAS palmitoyltransferases by accessory proteins and palmitoylation
Anlan Yang•Shengjie Liu•Yuqi Zhang•Jia Chen•Yujing Fan等 10 人
Nature Structural & Molecular Biology
2024
•2024/1/5
•00 p.1-11
Palmitoylation of cysteine residues at the C-terminal hypervariable regions in human HRAS and NRAS, which is necessary for RAS signaling, is catalyzed by the acyltransferase DHHC9 in complex with its accessory protein GCP16. The molecular basis for the acyltransferase activity and the regulation of ...
Cryoelectron microscopyPost-translational modifications
10.1038/S41594-023-01183-5
ISSN:1545-9993
Licensed H5N1 vaccines generate cross-neutralizing antibodies against highly pathogenic H5N1 clade 2.3.4.4b influenza virus
Surender Khurana•Lisa R. King•Jody Manischewitz•Olivia Posadas•Ashish K. Mishra等 10 人
Nature Medicine
2024
•2024/7/16
•00 p.1-6
The emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses and their transmission to dairy cattle and animals, including humans, poses a major global public health threat. Therefore, the development of effective vaccines and therapeutics against H5N1 clade 2.3.4.4b virus i...
Inactivated vaccinesInfluenza virus
10.1038/S41591-024-03189-Y
ISSN:1078-8956
Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia
Adriana E. Tron•Matthew A. Belmonte•Ammar Adam•Brian M. Aquila•Lawrence H. Boise等 34 人
Nature Communications
2018
•2018/12/17
•Vol.9 No.1 p.1-14
Mcl-1 is a member of the Bcl-2 family of proteins that promotes cell survival by preventing induction of apoptosis in many cancers. High expression of Mcl-1 causes tumorigenesis and resistance to anticancer therapies highlighting the potential of Mcl-1 inhibitors as anticancer drugs. Here, we descri...
Acute myeloid leukaemiaDrug discovery and developmentMyelomaStructure-based drug design
10.1038/S41467-018-07551-W
ISSN:2041-1723
A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites
Dimuthu Angage•Jill Chmielewski•Janesha C. Maddumage•Eva Hesping•Sabrina Caiazzo等 17 人
Nature Communications
2024
•2024/8/22
•Vol.15 No.1 p.1-17
Apical membrane antigen-1 (AMA1) is a conserved malarial vaccine candidate essential for the formation of tight junctions with the rhoptry neck protein (RON) complex, enabling Plasmodium parasites to invade human erythrocytes, hepatocytes, and mosquito salivary glands. Despite its critical role, ext...
Antibody fragment therapyMalariaParasite immune evasion
10.1038/S41467-024-50770-7
ISSN:2041-1723
Structure and mechanism of the mitochondrial Ca 2+ uniporter holocomplex
Minrui Fan•Jinru Zhang•Chen-Wei Tsai•Benjamin J. Orlando•Madison Rodriguez等 9 人
Nature
2020
•2020/5/20
•Vol.582 No.7810 p.129-133
Mitochondria take up Ca2+ through the mitochondrial calcium uniporter complex to regulate energy production, cytosolic Ca2+ signalling and cell death1,2. In mammals, the uniporter complex (uniplex) contains four core components: the pore-forming MCU protein, the gatekeepers MICU1 and MICU2, and an a...
Calcium channelsCryoelectron microscopy
10.1038/S41586-020-2309-6
ISSN:0028-0836
UDP-glucuronate metabolism controls RIPK1-driven liver damage in nonalcoholic steatohepatitis
Tao Zhang•Na Zhang•Jing Xing•Shuhua Zhang•Yulu Chen等 7 人
Nature Communications
2023
•2023/5/11
•Vol.14 No.1 p.1-18
Hepatocyte apoptosis plays an essential role in the progression of nonalcoholic steatohepatitis (NASH). However, the molecular mechanisms underlying hepatocyte apoptosis remain unclear. Here, we identify UDP-glucose 6-dehydrogenase (UGDH) as a suppressor of NASH-associated liver damage by inhibiting...
ApoptosisMechanisms of diseaseMetabolic disorders
10.1038/S41467-023-38371-2
ISSN:2041-1723
Structural basis for allosteric regulation of mycobacterial guanosine 5´-monophosphate reductase by ATP and GTP
Michal Doležal•Zdeněk Knejzlík•Tomáš Kouba•Anatolij Filimoněnko•Hana Šváchová等 8 人
Nature Communications
2026
•2026/4/13
0Guanosine 5′-monophosphate reductase (GMPR) is a crucial enzyme in the purine salvage pathway that catalyses the NADPH-dependent conversion of GMP to IMP, thereby contributing to purine nucleotide homeostasis. Mycobacterium smegmatis GMPR (MsmGMPR) contains a regulatory cystathionine β-synthase (CBS...
Cryoelectron microscopyEnzyme mechanismsNucleotide-binding proteinsX-ray crystallography
10.1038/S41467-026-71657-9
ISSN:2041-1723
Structural insight into the assembly and D antigenicity of polio type 1 stabilized virus-like particles
Qin Hong•Tian Chen•Wenyu Han•Shuxia Wang•Chaoyang Lian等 14 人
Npj Vaccines
2026
•2026/2/24
•Vol.11 No.1 p.790
The inherent instability of poliovirus capsids presents a formidable challenge for developing next-generation vaccines suitable for a post-eradication world. Here, we address this by engineering a thermally stabilized virus-like particle (sVLP) derived from the poliovirus serotype 1 (PV1) Mahoney-SC...
BiotechnologyImmunologyMicrobiology
10.1038/S41541-026-01404-0
ISSN:2059-0105
Protein-templated ligand discovery via the selection of DNA-encoded dynamic libraries
Yu Zhou•Wenyin Shen•Ying Gao•Jianzhao Peng•Qingrong Li等 15 人
Nature Chemistry
2024
•2024/2/7
•00 p.1-13
DNA-encoded chemical libraries (DELs) have become a powerful technology platform in drug discovery. Dual-pharmacophore DELs display two sets of small molecules at the termini of DNA duplexes, thereby enabling the identification of synergistic binders against biological targets, and have been success...
Computational chemistryHigh-throughput screeningScreening
10.1038/S41557-024-01442-Y
ISSN:1755-4330
Methanotrophic Methanoperedens archaea host diverse and interacting extrachromosomal elements
Ling-Dong Shi•Jacob West-Roberts•Marie C. Schoelmerich•Petar I. Penev•LinXing Chen等 9 人
Nature Microbiology
2024
•2024/6/25
•00 p.1-12
Methane emissions are mitigated by anaerobic methane-oxidizing archaea, including Methanoperedens. Some Methanoperedens host huge extrachromosomal genetic elements (ECEs) called Borgs that may modulate their activity, yet the broader diversity of Methanoperedens ECEs is understudied. Here we report ...
BiodiversityEnvironmental sciencesMicrobiology
10.1038/S41564-024-01740-8
ISSN:2058-5276
Structural basis of RNA polymerase complexes in African swine fever virus
Guoliang Zhu•Fei Xi•Wuxia Zeng•Yifei Zhao•Weijun Cao等 26 人
Nature Communications
2025
•2025/1/8
•Vol.16 No.1 p.1-13
African swine fever virus is highly contagious and causes a fatal infectious disease in pigs, resulting in a significant global impact on pork supply. The African swine fever virus RNA polymerase serves as a crucial multifunctional protein complex responsible for genome transcription and regulation....
Cryoelectron microscopyTranscriptionVirus structures
10.1038/S41467-024-55683-Z
ISSN:2041-1723
The Psu protein of phage satellite P4 inhibits transcription termination factor ρ by forced hyper-oligomerization
Daniela Gjorgjevikj•Naveen Kumar•Bing Wang•Tarek Hilal•Nelly Said等 9 人
Nature Communications
2025
•2025/1/9
•Vol.16 No.1 p.1-20
Many bacteriophages modulate host transcription to favor expression of their own genomes. Phage satellite P4 polarity suppression protein, Psu, a building block of the viral capsid, inhibits hexameric transcription termination factor, ρ, by presently unknown mechanisms. Our cryogenic electron micros...
BacteriophagesCryoelectron microscopyEnzyme mechanismsTranscription factorsTranscriptional regulatory elements
10.1038/S41467-025-55897-9
ISSN:2041-1723
A peptide-centric local stability assay enables proteome-scale identification of the protein targets and binding regions of diverse ligands
Kejia Li•Shijie Chen•Keyun Wang•Yan Wang•Lianji Xue等 20 人
Nature Methods
2024
•2024/12/10
•00 p.1-5
By using a limited-proteolysis strategy that employs a large amount of trypsin to generate peptides directly from native proteins, we found that ligand-induced protein local stability shifts can be sensitively detected on a proteome-wide scale. This enabled us to develop the peptide-centric local st...
Drug discoveryMass spectrometryProteomic analysisProteomics
10.1038/S41592-024-02553-7
ISSN:1548-7091
Quantifying constraint in the human mitochondrial genome
Nicole J. Lake•Kaiyue Ma•Wei Liu•Stephanie L. Battle•Kristen M. Laricchia等 17 人
Nature
2024
•2024/10/16
•00 p.1-8
Mitochondrial DNA (mtDNA) has an important yet often overlooked role in health and disease. Constraint models quantify the removal of deleterious variation from the population by selection and represent powerful tools for identifying genetic variation that underlies human phenotypes1–4. However, nuc...
Computational modelsDisease geneticsEvolutionary geneticsPopulation genetics
10.1038/S41586-024-08048-X
ISSN:0028-0836
Functionally selective signaling and broad metabolic benefits by novel insulin receptor partial agonists
Wu Margaret•Carballo-Jane Ester•Zhou Haihong•Zafian Peter•Dai Ge等 25 人
Nature Communications
2022
•2022/2/17
•Vol.13 No.1 p.1-15
Insulin analogs have been developed to treat diabetes with focus primarily on improving the time action profile without affecting ligand-receptor interaction or functional selectivity. As a result, inherent liabilities (e.g. hypoglycemia) of injectable insulin continue to limit the true therapeutic ...
Receptor pharmacologyType 2 diabetes
10.1038/S41467-022-28561-9
ISSN:2041-1723
Probing ion channel functional architecture and domain recombination compatibility by massively parallel domain insertion profiling
Coyote-Maestas Willow•Nedrud David•Suma Antonio•He Yungui•Matreyek Kenneth A.等 9 人
Nature Communications
2021
•2021/12/8
•Vol.12 No.1 p.1-16
Protein domains are the basic units of protein structure and function. Comparative analysis of genomes and proteomes showed that domain recombination is a main driver of multidomain protein functional diversification and some of the constraining genomic mechanisms are known. Much less is known about...
Molecular biophysicsPotassium channelsProtein design
10.1038/S41467-021-27342-0
ISSN:2041-1723
Phage defence system CBASS is regulated by a prokaryotic E2 enzyme that imitates the ubiquitin pathway
Yan Yan•Jun Xiao•Fengtao Huang•Wei Xian•Bingbing Yu等 18 人
Nature Microbiology
2024
•2024/4/22
•00 p.1-13
The cyclic-oligonucleotide-based anti-phage signalling system (CBASS) is a type of innate prokaryotic immune system. Composed of a cyclic GMP–AMP synthase (cGAS) and CBASS-associated proteins, CBASS uses cyclic oligonucleotides to activate antiviral immunity. One major class of CBASS contains a homo...
Enzyme mechanismsPhage biologyUbiquitylation
10.1038/S41564-024-01684-Z
ISSN:2058-5276
Novel sarbecovirus bispecific neutralizing antibodies with exceptional breadth and potency against currently circulating SARS-CoV-2 variants and sarbecoviruses
Wang Yingdan•Liu Meiqin•Shen Yaping•Ma Yunping•Li Xiang等 26 人
Cell Discovery
2022
•2022/4/21
•Vol.8 No.1 p.1-16
The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) has aroused concerns over their increased infectivity and transmissibility, as well as decreased sensi...
AutoimmunityCryoelectron microscopyMechanisms of disease
10.1038/S41421-022-00401-6
ISSN:2056-5968
Structure-based investigation of fluorogenic Pepper aptamer
Huang Kaiyi•Chen Xianjun•Li Chunyan•Song Qianqian•Li Huiwen等 8 人
Nature Chemical Biology
2021
•2021/11/1
•00 p.1-7
Pepper fluorescent RNAs are a recently reported bright, stable and multicolor fluorogenic aptamer tag that enable imaging of diverse RNAs in live cells. To investigate the molecular basis of the superior properties of Pepper, we determined the structures of complexes of Pepper aptamer bound with its...
ImagingNucleic acidsRNAX-ray crystallography
10.1038/S41589-021-00884-6
ISSN:1552-4450
Diadenosine tetraphosphate regulates biosynthesis of GTP in Bacillus subtilis
Giammarinaro Pietro I.•Young Megan K. M.•Steinchen Wieland•Mais Christopher-Nils•Hochberg Georg等 11 人
Nature Microbiology
2022
•2022/8/11
•00 p.1-11
Diadenosine tetraphosphate (Ap4A) is a putative second messenger molecule that is conserved from bacteria to humans. Nevertheless, its physiological role and the underlying molecular mechanisms are poorly characterized. We investigated the molecular mechanism by which Ap4A regulates inosine-5′-monop...
Applied microbiologyMicrobiology
10.1038/S41564-022-01193-X
ISSN:2058-5276
Transcriptional processing of an unnatural base pair by eukaryotic RNA polymerase II
Juntaek Oh•Ji Shin•Ilona Christy Unarta•Wei Wang•Aaron W. Feldman等 13 人
Nature Chemical Biology
2021
•2021/6/17
•00 p.1-9
The development of unnatural base pairs (UBPs) has greatly increased the information storage capacity of DNA, allowing for transcription of unnatural RNA by the heterologously expressed T7 RNA polymerase (RNAP) in Escherichia coli. However, little is known about how UBPs are transcribed by cellular ...
Enzyme mechanismsSynthetic biologyX-ray crystallography
10.1038/S41589-021-00817-3
ISSN:1552-4450
Structural basis for aerobic anoxygenic photosynthesis in the reaction center–light-harvesting 1 (RC–LH1) supercomplex of Dinoroseobacter shibae
Ze-Kun Liu•Jian-Xun Li•Ying-Yue Zhang•Jing-Li Lv•Kang Li等 9 人
Communications Biology
2025
•2025/11/14
•Vol.8 No.1 p.15650
Aerobic anoxygenic phototrophic (AAP) bacteria are essential for oceanic carbon cycling. However, their architecture and structural adaptations of their photosynthetic systems to ensure adequate light harvesting, electron transport, and oxidative resilience in oxygen-rich environments remain poorly ...
Cryoelectron microscopyPhotosynthesis
10.1038/S42003-025-08935-7
ISSN:2399-3642
Structure of the human marker of self 5-transmembrane receptor CD47
Fenalti Gustavo•Villanueva Nicolas•Griffith Mark•Pagarigan Barbra•Lakkaraju Sirish Kaushik等 16 人
Nature Communications
2021
•2021/9/1
•Vol.12 No.1 p.1-14
CD47 is the only 5-transmembrane (5-TM) spanning receptor of the immune system. Its extracellular domain (ECD) is a cell surface marker of self that binds SIRPα and inhibits macrophage phagocytosis, and cancer immuno-therapy approaches in clinical trials are focused on blocking CD47/SIRPα interactio...
Membrane proteinsSignal transductionX-ray crystallography
10.1038/S41467-021-25475-W
ISSN:2041-1723
DPFunc: accurately predicting protein function via deep learning with domain-guided structure information
Wenkang Wang•Yunyan Shuai•Min Zeng•Wei Fan•Min Li
Nature Communications
2025
•2025/1/2
•Vol.16 No.1 p.1-13
Computational methods for predicting protein function are of great significance in understanding biological mechanisms and treating complex diseases. However, existing computational approaches of protein function prediction lack interpretability, making it difficult to understand the relations betwe...
Gene ontologyMachine learningProtein function predictionsProtein structure predictionsSequence annotation
10.1038/S41467-024-54816-8
ISSN:2041-1723
REDD1 promotes obesity-induced metabolic dysfunction via atypical NF-κB activation
Lee Dong-Keon•Kim Taesam•Byeon Junyoung•Park Minsik•Kim Suji等 14 人
Nature Communications
2022
•2022/10/22
•Vol.13 No.1 p.1-16
Regulated in development and DNA damage response 1 (REDD1) expression is upregulated in response to metabolic imbalance and obesity. However, its role in obesity-associated complications is unclear. Here, we demonstrate that the REDD1–NF-κB axis is crucial for metabolic inflammation and dysregulatio...
Cell biologyMetabolismMolecular biologyObesity
10.1038/S41467-022-34110-1
ISSN:2041-1723
Discovery of isoquinoline sulfonamides as allosteric gyrase inhibitors with activity against fluoroquinolone-resistant bacteria
Alexander T. Bakker•Ioli Kotsogianni•Mariana Avalos•Jeroen M. Punt•Bing Liu等 19 人
Nature Chemistry
2024
•2024/6/19
•00 p.1-11
Bacteria have evolved resistance to nearly all known antibacterials, emphasizing the need to identify antibiotics that operate via novel mechanisms. Here we report a class of allosteric inhibitors of DNA gyrase with antibacterial activity against fluoroquinolone-resistant clinical isolates of Escher...
AntibioticsCryoelectron microscopyTarget identification
10.1038/S41557-024-01516-X
ISSN:1755-4330
Autoregulation of GPCR signalling through the third intracellular loop
Sadler Fredrik•Ma Ning•Ritt Michael•Sharma Yatharth•Vaidehi Nagarajan等 6 人
Nature
2023
•2023/3/8
•Vol.615 No.7953 p.734-741
The third intracellular loop (ICL3) of the G protein-coupled receptor (GPCR) fold is important for the signal transduction process downstream of receptor activation1–3. Despite this, the lack of a defined structure of ICL3, combined with its high sequence divergence among GPCRs, complicates cha...
Cell signallingMechanism of action
10.1038/S41586-023-05789-Z
ISSN:0028-0836
Recognition of host Clr-b by the inhibitory NKR-P1B receptor provides a basis for missing-self recognition
Gautham R. Balaji•Oscar A. Aguilar•Miho Tanaka•Miguel A. Shingu-Vazquez•Zhihui Fu等 10 人
Nature Communications
2018
•2018/11/5
•Vol.9 No.1 p.1-12
The interaction between natural killer (NK) cell inhibitory receptors and their cognate ligands constitutes a key mechanism by which healthy tissues are protected from NK cell-mediated lysis. However, self-ligand recognition remains poorly understood within the prototypical NKR-P1 receptor family. H...
AutoimmunityInnate lymphoid cellsSignal transductionX-ray crystallography
10.1038/S41467-018-06989-2
ISSN:2041-1723
Structural basis underlying the synergism of NADase and SLO during group A Streptococcus infection
Tsai Wei-Jiun•Lai Yi-Hsin•Shi Yong-An•Hammel Michal•Duff Anthony P.等 20 人
Communications Biology
2023
•2023/1/31
•Vol.6 No.1 p.1-12
Group A Streptococcus (GAS) is a strict human pathogen possessing a unique pathogenic trait that utilizes the cooperative activity of NAD+-glycohydrolase (NADase) and Streptolysin O (SLO) to enhance its virulence. How NADase interacts with SLO to synergistically promote GAS cytotoxicity and intracel...
Bacterial pathogenesisBacterial toxinsSAXSX-ray crystallography
10.1038/S42003-023-04502-0
ISSN:2399-3642
Acetylation-dependent coupling between G6PD activity and apoptotic signaling
Fang Wu•Natali H. Muskat•Inbar Dvilansky•Omri Koren•Anat Shahar等 8 人
Nature Communications
2023
•2023/10/5
•Vol.14 No.1 p.1-18
Lysine acetylation has been discovered in thousands of non-histone human proteins, including most metabolic enzymes. Deciphering the functions of acetylation is key to understanding how metabolic cues mediate metabolic enzyme regulation and cellular signaling. Glucose-6-phosphate dehydrogenase (G6PD...
AcetylationEnzymesX-ray crystallography
10.1038/S41467-023-41895-2
ISSN:2041-1723
Structure of trypanosome coat protein VSGsur and function in suramin resistance
Johan Zeelen•Monique van Straaten•Joseph Verdi•Alexander Hempelmann•Hamidreza Hashemi等 12 人
Nature Microbiology
2021
•2021/1/18
•Vol.6 No.3 p.392-400
Suramin has been a primary early-stage treatment for African trypanosomiasis for nearly 100 yr. Recent studies revealed that trypanosome strains that express the variant surface glycoprotein (VSG) VSGsur possess heightened resistance to suramin. Here, we show that VSGsur binds tightly to suramin but...
AntimicrobialsParasite immune evasionX-ray crystallography
10.1038/S41564-020-00844-1
ISSN:2058-5276
Single-molecule dynamics reveal ATP binding alone powers substrate translocation by an ABC transporter
Christoph Nocker•Matija Pečak•Tobias Nocker•Amin Fahim•Lukas Sušac等 6 人
Nature Communications
2026
•2026/3/31
•Vol.17 No.1 p.30380
ATP-binding cassette (ABC) transporters are molecular machines involved in diverse physiological processes, including antigen processing by TAP, a key component of adaptive immunity. TAP and its bacterial homolog TmrAB use ATP to translocate peptides across membranes, yet the precise mechanism linki...
Cryoelectron microscopyMembrane proteinsSingle-molecule biophysics
10.1038/S41467-026-70021-1
ISSN:2041-1723
Structural basis for the regulation of plant transcription factor WRKY33 by the VQ protein SIB1
Xu Dong•Lulu Yu•Qiang Zhang•Ju Yang•Zhou Gong等 11 人
Communications Biology
2024
•2024/5/11
•Vol.7 No.1 p.1-11
The WRKY transcription factors play essential roles in a variety of plant signaling pathways associated with biotic and abiotic stress response. The transcriptional activity of many WRKY members are regulated by a class of intrinsically disordered VQ proteins. While it is known that VQ proteins inte...
Intrinsically disordered proteinsSolution-state NMR
10.1038/S42003-024-06258-7
ISSN:2399-3642
Population-specific putative causal variants shape quantitative traits
Satoshi Koyama•Xiaoxi Liu•Yoshinao Koike•Keiko Hikino•Masaru Koido等 30 人
Nature Genetics
2024
•2024/10/3
•00 p.1-9
Human genetic variants are associated with many traits through largely unknown mechanisms. Here, combining approximately 260,000 Japanese study participants, a Japanese-specific genotype reference panel and statistical fine-mapping, we identified 4,423 significant loci across 63 quantitative traits,...
Genome-wide association studiesPersonalized medicine
10.1038/S41588-024-01913-5
ISSN:1061-4036
Inhibitory efficacy and structural insights of Bofutrelvir against SARS-CoV-2 Mpro mutants and MERS-CoV Mpro
Weiwei Wang•Xuelan Zhou•Wenwen Li•Pei Zeng•Li Guo等 7 人
Communications Biology
2025
•2025/3/25
•Vol.8 No.1 p.1-13
The COVID-19 pandemic has caused significant global health and economic disruption. Mutations E166N, E166R, E166N, S144A and His163A in the SARS-CoV-2 main protease (Mpro) have been implicated in reducing the efficacy of certain antiviral treatments. Bofutrelvir, a promising inhibitor, has shown eff...
SARS-CoV-2X-ray crystallography
10.1038/S42003-025-07929-9
ISSN:2399-3642
Large protein-like leader peptides engage differently with RiPP halogenases and lanthionine synthetases
FNU Vidya•Youran Luo•Hongwei Wu•Wilfred A. van der Donk•Andrew C. McShan等 6 人
Nature Communications
2025
•2025/10/20
•Vol.16 No.1 p.1-15
The biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs) involves binding of the N-terminal leader region of precursor peptides to peptide-modifying enzymes and subsequent modification of the C-terminal core. Canonical RiPP leaders are short and unstructured. Ho...
BiocatalysisMass spectrometryMolecular biophysicsNatural product synthesisPeptides
10.1038/S41467-025-64365-3
ISSN:2041-1723
Expanded phylogeny of extremely halophilic archaea shows multiple independent adaptations to hypersaline environments
Brittany A. Baker•Ana Gutiérrez-Preciado•Álvaro Rodríguez del Río•Charley G. P. McCarthy•Purificación López-García等 10 人
Nature Microbiology
2024
•2024/3/22
•00 p.1-12
Extremely halophilic archaea (Haloarchaea, Nanohaloarchaeota, Methanonatronarchaeia and Halarchaeoplasmatales) thrive in saturating salt concentrations where they must maintain osmotic equilibrium with their environment. The evolutionary history of adaptations enabling salt tolerance remains poorly ...
ArchaeaMolecular evolutionPhylogenetics
10.1038/S41564-024-01647-4
ISSN:2058-5276
Kinetic mechanism of Na+-coupled aspartate transport catalyzed by GltTk
Gianluca Trinco•Valentina Arkhipova•Alisa A. Garaeva•Cedric A. J. Hutter•Markus A. Seeger等 7 人
Communications Biology
2021
•2021/6/17
•Vol.4 No.1 p.1-11
It is well-established that the secondary active transporters GltTk and GltPh catalyze coupled uptake of aspartate and three sodium ions, but insight in the kinetic mechanism of transport is fragmentary. Here, we systematically measured aspartate uptake rates in proteoliposomes containing purified G...
Cryoelectron microscopyMembrane proteins
10.1038/S42003-021-02267-Y
ISSN:2399-3642
Molecular basis of human taurine transporter uptake and inhibition
Bowen Du•Lili Cheng•Jiaying Xie•Ligong Chen•Kaige Yan
Nature Communications
2025
•2025/8/11
•Vol.16 No.1 p.1-12
The taurine transporter, TauT, regulates various taurine-mediated physiological and pathological functions by facilitating taurine uptake in a sodium- and chloride-dependent manner. Dysfunction of TauT is associated with male infertility, retinal health and cancers. Despite extensive research effort...
Cryoelectron microscopyElectron microscopyMolecular biophysics
10.1038/S41467-025-62857-W
ISSN:2041-1723