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380Contact-independent killing mediated by a T6SS effector with intrinsic cell-entry properties
Li Song•Junfeng Pan•Yantao Yang•Zhenxing Zhang•Rui Cui等 12 人
Nature Communications
2021
•2021/1/18
•Vol.12 No.1 p.1-12
Bacterial type VI secretion systems (T6SSs) inject toxic effectors into adjacent eukaryotic and prokaryotic cells. It is generally thought that this process requires physical contact between the two cells. Here, we provide evidence of contact-independent killing by a T6SS-secreted effector. We show ...
Bacterial secretionBacterial toxinsMicrobial ecology
10.1038/S41467-020-20726-8
ISSN:2041-1723
Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut
Laursen Martin F.•Sakanaka Mikiyasu•von Burg Nicole•Mörbe Urs•Andersen Daniel等 20 人
Nature Microbiology
2021
•2021/10/21
•00 p.1-16
Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host–mic...
EnzymesMetabolomicsMicrobial ecologyMicrobiome
10.1038/S41564-021-00970-4
ISSN:2058-5276
Proteomics of protein trafficking by in vivo tissue-specific labeling
Ilia A. Droujinine•Amanda S. Meyer•Dan Wang•Namrata D. Udeshi•Yanhui Hu等 21 人
Nature Communications
2021
•2021/4/22
•Vol.12 No.1 p.1-22
Conventional approaches to identify secreted factors that regulate homeostasis are limited in their abilities to identify the tissues/cells of origin and destination. We established a platform to identify secreted protein trafficking between organs using an engineered biotin ligase (BirA*G3) that bi...
CirculationExtracellular signalling moleculesProteomic analysisProteomics
10.1038/S41467-021-22599-X
ISSN:2041-1723
DeepPhospho accelerates DIA phosphoproteome profiling through in silico library generation
Lou Ronghui•Liu Weizhen•Li Rongjie•Li Shanshan•He Xuming等 6 人
Nature Communications
2021
•2021/11/18
•Vol.12 No.1 p.1-15
Phosphoproteomics integrating data-independent acquisition (DIA) enables deep phosphoproteome profiling with improved quantification reproducibility and accuracy compared to data-dependent acquisition (DDA)-based phosphoproteomics. DIA data mining heavily relies on a spectral library that in most ca...
Machine learningPhosphorylationProteome informaticsProteomics
10.1038/S41467-021-26979-1
ISSN:2041-1723
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
Explainable deep learning and virtual evolution identifies antimicrobial peptides with activity against multidrug-resistant human pathogens
Beilun Wang•Peijun Lin•Yuwei Zhong•Xiao Tan•Yangyang Shen等 13 人
Nature Microbiology
2025
•2025/1/17
•00 p.1-16
Artificial intelligence (AI) is a promising approach to identify new antimicrobial compounds in diverse microbial species. Here we developed an AI-based, explainable deep learning model, EvoGradient, that predicts the potency of antimicrobial peptides (AMPs) and virtually modifies peptide sequences ...
AntimicrobialsDrug developmentMachine learning
10.1038/S41564-024-01907-3
ISSN:2058-5276
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
Identification of potent antimicrobial peptides via a machine-learning pipeline that mines the entire space of peptide sequences
Huang Junjie•Xu Yanchao•Xue Yunfan•Huang Yue•Li Xu等 11 人
Nature Biomedical Engineering
2023
•2023/1/12
•00 p.1-14
Systematically identifying functional peptides is difficult owing to the vast combinatorial space of peptide sequences. Here we report a machine-learning pipeline that mines the hundreds of billions of sequences in the entire virtual library of peptides made of 6–9 amino acids to identify potent ant...
Computational scienceHigh-throughput screeningMachine learning
10.1038/S41551-022-00991-2
ISSN:2157-846X
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
Novel coenzyme Q6 genetic variant increases susceptibility to pneumococcal disease
Emma C. Walker•Sarah Javati•Elizabeth M. Todd•John-Paul Matlam•Xue Lin等 30 人
Nature Immunology
2024
•2024/11/4
•00 p.1-12
Acute lower respiratory tract infection (ALRI) remains a major worldwide cause of childhood mortality, compelling innovation in prevention and treatment. Children in Papua New Guinea (PNG) experience profound morbidity from ALRI caused by Streptococcus pneumoniae. As a result of evolutionary diverge...
Antimicrobial responsesBacterial infectionInfection
10.1038/S41590-024-01998-4
ISSN:1529-2908
Gonococcal OMV-delivered PorB induces epithelial cell mitophagy
Shuai Gao•Lingyu Gao•Dailin Yuan•Xu’ai Lin•Stijn van der Veen
Nature Communications
2024
•2024/2/23
•Vol.15 No.1 p.1-15
The bacterial pathogen Neisseria gonorrhoeae is able to invade epithelial cells and survive intracellularly. During this process, it secretes outer membrane vesicles (OMVs), however, the mechanistic details for interactions between gonococcal OMVs and epithelial cells and their impact on intracellul...
BacteriologyCellular microbiology
10.1038/S41467-024-45961-1
ISSN:2041-1723
Identification of gene function based on models capturing natural variability of Arabidopsis thaliana lipid metabolism
Sandra Correa Córdoba•Hao Tong•Asdrúbal Burgos•Feng Zhu•Saleh Alseekh等 7 人
Nature Communications
2023
•2023/8/14
•Vol.14 No.1 p.1-12
Lipids play fundamental roles in regulating agronomically important traits. Advances in plant lipid metabolism have until recently largely been based on reductionist approaches, although modulation of its components can have system-wide effects. However, existing models of plant lipid metabolism pro...
Biochemical networksBiochemical reaction networksGenetic modelsPlant molecular biology
10.1038/S41467-023-40644-9
ISSN:2041-1723
SETD2 deficiency accelerates sphingomyelin accumulation and promotes the development of renal cancer
Hanyu Rao•Changwei Liu•Aiting Wang•Chunxiao Ma•Yue Xu等 11 人
Nature Communications
2023
•2023/11/21
•Vol.14 No.1 p.1-15
Patients with polycystic kidney disease (PKD) encounter a high risk of clear cell renal cell carcinoma (ccRCC), a malignant tumor with dysregulated lipid metabolism. SET domain–containing 2 (SETD2) has been identified as an important tumor suppressor and an immunosuppressor in ccRCC. However, the ro...
Cancer metabolismProteomic analysisRenal cell carcinomaTumour-suppressor proteins
10.1038/S41467-023-43378-W
ISSN:2041-1723
Immunopeptidomics-based identification of naturally presented non-canonical circRNA-derived peptides
Humberto J. Ferreira•Brian J. Stevenson•HuiSong Pak•Fengchao Yu•Jessica Almeida Oliveira等 15 人
Nature Communications
2024
•2024/3/15
•Vol.15 No.1 p.1-18
Circular RNAs (circRNAs) are covalently closed non-coding RNAs lacking the 5’ cap and the poly-A tail. Nevertheless, it has been demonstrated that certain circRNAs can undergo active translation. Therefore, aberrantly expressed circRNAs in human cancers could be an unexplored source of tumor-specifi...
Antigen processing and presentationTumour immunology
10.1038/S41467-024-46408-3
ISSN:2041-1723
DNA-driven condensation assembles the meiotic DNA break machinery
Corentin Claeys Bouuaert•Stephen Pu•Juncheng Wang•Cédric Oger•Dima Daccache等 8 人
Nature
2021
•2021/3/17
•Vol.592 No.7852 p.144-149
The accurate segregation of chromosomes during meiosis—which is critical for genome stability across sexual cycles—relies on homologous recombination initiated by DNA double-strand breaks (DSBs) made by the Spo11 protein1,2. The formation of DSBs is regulated and tied to the elaboration of large-sca...
DNA-binding proteinsDNA recombinationMeiosis
10.1038/S41586-021-03374-W
ISSN:0028-0836
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
Microbiome-mediated fructose depletion restricts murine gut colonization by vancomycin-resistant Enterococcus
Isaac Sandrine•Flor-Duro Alejandra•Carruana Gloria•Puchades-Carrasco Leonor•Quirant Anna等 9 人
Nature Communications
2022
•2022/12/13
•Vol.13 No.1 p.1-19
Multidrug-resistant organisms (MDRO) are a major threat to public health. MDRO infections, including those caused by vancomycin-resistant Enterococcus (VRE), frequently begin by colonization of the intestinal tract, a crucial step that is impaired by the intestinal microbiota. However, the specific ...
Microbial communitiesInfectionPathogens
10.1038/S41467-022-35380-5
ISSN:2041-1723
Latent generative landscapes as maps of functional diversity in protein sequence space
Ziegler Cheyenne•Martin Jonathan•Sinner Claude•Morcos Faruck
Nature Communications
2023
•2023/4/19
•Vol.14 No.1 p.1-15
Variational autoencoders are unsupervised learning models with generative capabilities, when applied to protein data, they classify sequences by phylogeny and generate de novo sequences which preserve statistical properties of protein composition. While previous studies focus on clustering and gener...
Computational biophysicsFunctional clusteringMachine learningProtein design
10.1038/S41467-023-37958-Z
ISSN:2041-1723
Ab-initio amino acid sequence design from protein text description with ProtDAT
Xiao-Yu Guo•Yi-Fan Li•Yuan Liu•Xiaoyong Pan•Hong-Bin Shen
Nature Communications
2025
•2025/11/26
•Vol.16 No.1 p.105440
Protein design has become a critical method in advancing significant potential for various applications such as drug development and enzyme engineering. However, protein design methods utilizing large language models with solely pretraining and fine-tuning struggle to capture relationships in multi-...
Machine learningProtein designProtein structure predictions
10.1038/S41467-025-65562-W
ISSN:2041-1723
Mirror-image trypsin digestion and sequencing of D-proteins
Guanwei Zhang•Ting F. Zhu
Nature Chemistry
2024
•2024/1/18
•00 p.1-7
The development of mirror-image biology systems and related applications is hindered by the lack of effective methods to sequence mirror-image (D-) proteins. Although natural-chirality (L-) proteins can be sequenced by bottom–up liquid chromatography–tandem mass spectrometry (LC–MS/MS), the sequenci...
Protein sequencingProteinsChemical synthesis
10.1038/S41557-023-01411-X
ISSN:1755-4330
Bioorthogonal photocatalytic proximity labeling in primary living samples
Ziqi Liu•Fuhu Guo•Yufan Zhu•Shengnan Qin•Yuchen Hou等 9 人
Nature Communications
2024
•2024/3/28
•Vol.15 No.1 p.1-18
In situ profiling of subcellular proteomics in primary living systems, such as native tissues or clinic samples, is crucial for understanding life processes and diseases, yet challenging due to methodological obstacles. Here we report CAT-S, a bioorthogonal photocatalytic chemistry-enabled proximity...
Chemical toolsMitochondrial proteinsPhotocatalysisProteomics
10.1038/S41467-024-46985-3
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
PilY1 and minor pilins form a complex priming the type IVa pilus in Myxococcus xanthus
Anke Treuner-Lange•Yi-Wei Chang•Timo Glatter•Marco Herfurth•Steffi Lindow等 8 人
Nature Communications
2020
•2020/10/7
•Vol.11 No.1 p.1-14
Type IVa pili are ubiquitous and versatile bacterial cell surface filaments that undergo cycles of extension, adhesion and retraction powered by the cell-envelope spanning type IVa pilus machine (T4aPM). The overall architecture of the T4aPM and the location of 10 conserved core proteins within this...
Bacterial structural biologyCellular microbiologyCryoelectron tomography
10.1038/S41467-020-18803-Z
ISSN:2041-1723
Segatella copri and gut microbial ammonia metabolism contribute to chronic kidney disease pathogenesis
Shuchun Lin•Zhonghan Sun•Xinna Zhu•Mengjing Wang•Qian Zhang等 23 人
Nature Microbiology
2025
•2025/6/24
•Vol.10 No.7 p.1684-1697
Alterations in gut microbiota have been linked to chronic kidney disease (CKD), but large-scale studies and mechanistic insights are limited. Here we analysed gut metagenome data from 1,550 older individuals (aged 65–93 years) with comprehensive kidney function measurements. Segatella copri was posi...
Kidney diseasesMetagenomics
10.1038/S41564-025-02039-Y
ISSN:2058-5276
Structure-based validation can drastically underestimate error rate in proteome-wide cross-linking mass spectrometry studies
Kumar Yugandhar•Ting-Yi Wang•Shayne D. Wierbowski•Elnur Elyar Shayhidin•Haiyuan Yu
Nature Methods
2020
•2020/9/29
•Vol.17 No.10 p.985-988
Thorough quality assessment of novel interactions identified by proteome-wide cross-linking mass spectrometry (XL-MS) studies is critical. Almost all current XL-MS studies have validated cross-links against known three-dimensional structures of representative protein complexes. Here, we provide theo...
Mass spectrometryProtein–protein interaction networksProteome informaticsProteomic analysisSystems biology
10.1038/S41592-020-0959-9
ISSN:1548-7091
DeepDTAGen: a multitask deep learning framework for drug-target affinity prediction and target-aware drugs generation
Pir Masoom Shah•Huimin Zhu•Zhangli Lu•Kaili Wang•Jing Tang等 6 人
Nature Communications
2025
•2025/5/30
•Vol.16 No.1 p.1-15
Identifying novel drugs that can interact with target proteins is a highly challenging, time-consuming, and costly task in drug discovery and development. Numerous machine learning-based models have recently been utilized to accelerate the drug discovery process. However, these existing methods are ...
Computational modelsDrug screeningMachine learning
10.1038/S41467-025-59917-6
ISSN:2041-1723
Predicting nuclear G-quadruplex RNA-binding proteins with roles in transcription and phase separation
Johanna Luige•Alexandros Armaos•Gian Gaetano Tartaglia•Ulf Andersson Vang Ørom
Nature Communications
2024
•2024/3/22
•Vol.15 No.1 p.1-13
RNA-binding proteins are central for many biological processes and their characterization has demonstrated a broad range of functions as well as a wide spectrum of target structures. RNA G-quadruplexes are important regulatory elements occurring in both coding and non-coding transcripts, yet our kno...
Computational biology and bioinformaticsRNA
10.1038/S41467-024-46731-9
ISSN:2041-1723
Ubiquitination of RIPK1 regulates its activation mediated by TNFR1 and TLRs signaling in distinct manners
Xingyan Li•Mengmeng Zhang•Xinyue Huang•Wei Liang•Ganquan Li等 13 人
Nature Communications
2020
•2020/12/11
•Vol.11 No.1 p.1-18
RIPK1 is a death-domain (DD) containing kinase involved in regulating apoptosis, necroptosis and inflammation. RIPK1 activation is known to be regulated by its DD-mediated interaction and ubiquitination, though underlying mechanisms remain incompletely understood. Here we show that K627 in human RIP...
ApoptosisInflammatory diseasesNecroptosisUbiquitylation
10.1038/S41467-020-19935-Y
ISSN:2041-1723
The Ruminococcus bromii amylosome protein Sas6 binds single and double helical α-glucan structures in starch
Amanda L. Photenhauer•Rosendo C. Villafuerte-Vega•Filipe M. Cerqueira•Krista M. Armbruster•Filip Mareček等 12 人
Nature Structural & Molecular Biology
2024
•2024/1/4
•00 p.1-11
Resistant starch is a prebiotic accessed by gut bacteria with specialized amylases and starch-binding proteins. The human gut symbiont Ruminococcus bromii expresses Sas6 (Starch Adherence System member 6), which consists of two starch-specific carbohydrate-binding modules from family 26 (RbCBM26) an...
Cellular microbiologyGlycobiologyX-ray crystallography
10.1038/S41594-023-01166-6
ISSN:1545-9993
Analysis of Zika virus capsid- Aedes aegypti mosquito interactome reveals pro-viral host factors critical for establishing infection
Rommel J. Gestuveo•Jamie Royle•Claire L. Donald•Douglas J. Lamont•Edward C. Hutchinson等 8 人
Nature Communications
2021
•2021/5/13
•Vol.12 No.1 p.1-16
The escalating global prevalence of arboviral diseases emphasizes the need to improve our understanding of their biology. Research in this area has been hindered by the lack of molecular tools for studying virus-mosquito interactions. Here, we develop an Aedes aegypti cell line which stably expresse...
Cell biologyProtein–protein interaction networksVirus–host interactions
10.1038/S41467-021-22966-8
ISSN:2041-1723
Nanobody–antigen interaction prediction with ensemble deep learning and prompt-based protein language models
Juntao Deng•Miao Gu•Pengyan Zhang•Mingyu Dong•Tao Liu等 7 人
Nature Machine Intelligence
2024
•2024/12/5
•00 p.1-11
Nanobodies can provide specific binding to divergent antigens, leading to many promising therapeutic and detection applications in recent years. Traditional technologies of nanobody discovery based on alpaca immunization and phage display are very time-consuming and labour-intensive. Despite recent ...
Computational modelsMachine learningProtein function predictionsVirtual drug screening
10.1038/S42256-024-00940-5
ISSN:2522-5839
A host–microbiota interactome reveals extensive transkingdom connectivity
Nicole D. Sonnert•Connor E. Rosen•Andrew R. Ghazi•Eric A. Franzosa•Brianna Duncan-Lowey等 21 人
Nature
2024
•2024/3/20
•00 p.1-9
The myriad microorganisms that live in close association with humans have diverse effects on physiology, yet the molecular bases for these impacts remain mostly unknown1–3. Classical pathogens often invade host tissues and modulate immune responses through interactions with human extracellular and s...
Bacterial infectionImmune evasionMicrobiomeMucosal immunology
10.1038/S41586-024-07162-0
ISSN:0028-0836
Nanobody-thioesterase chimeras to specifically target protein palmitoylation
Chien-Wen Kuo•Caglar Gök•Hannah Fulton•Eleanor Dickson-Murray•Samuel Adu等 13 人
Nature Communications
2025
•2025/2/7
•Vol.16 No.1 p.1-13
The complexity of the cellular proteome is massively expanded by a repertoire of chemically distinct reversible post-translational modifications (PTMs) that control protein localisation, interactions, and function. The temporal and spatial control of these PTMs is central to organism physiology, and...
Calcium channelsEnzymesNanobiotechnologyPost-translational modifications
10.1038/S41467-025-56716-X
ISSN:2041-1723
An extracellular receptor tyrosine kinase motif orchestrating intracellular STAT activation
Vaparanta Katri•Jokilammi Anne•Tamirat Mahlet•Merilahti Johannes A. M.•Salokas Kari等 9 人
Nature Communications
2022
•2022/11/14
•Vol.13 No.1 p.1-19
The ErbB4 receptor isoforms JM-a and JM-b differ within their extracellular juxtamembrane (eJM) domains. Here, ErbB4 isoforms are used as a model to address the effect of structural variation in the eJM domain of receptor tyrosine kinases (RTK) on downstream signaling. A specific JM-a-like sequence ...
Extracellular signalling moleculesGrowth factor signallingProtein–protein interaction networks
10.1038/S41467-022-34539-4
ISSN:2041-1723
Recruitment of Cdc48 to chloroplasts by a UBX-domain protein in chloroplast-associated protein degradation
Na Li•R. Paul Jarvis
Nature Plants
2024
•2024/8/19
•00 p.1-18
The translocon at the outer chloroplast membrane (TOC) is the gateway for chloroplast protein import and so is vital for photosynthetic establishment and plant growth. Chloroplast-associated protein degradation (CHLORAD) is a ubiquitin-dependent proteolytic system that regulates TOC. In CHLORAD, cyt...
Cell biologyChloroplastsProtein trafficking in plantsProteolysis in plantsTransgenic plants
10.1038/S41477-024-01769-X
ISSN:2055-0278
A protein kinase coordinates cycles of autophagy and glutaminolysis in invasive hyphae of the fungus Magnaporthe oryzae within rice cells
Gang Li•Ziwen Gong•Nawaraj Dulal•Margarita Marroquin-Guzman•Raquel O. Rocha等 7 人
Nature Communications
2023
•2023/7/12
•Vol.14 No.1 p.1-15
The blast fungus Magnaporthe oryzae produces invasive hyphae in living rice cells during early infection, separated from the host cytoplasm by plant-derived interfacial membranes. However, the mechanisms underpinning this intracellular biotrophic growth phase are poorly understood. Here, we show tha...
AutophagyCellular microbiologyFungal pathogenesisParasitismPathogens
10.1038/S41467-023-39880-W
ISSN:2041-1723
A CRISPR activation screen identifies FBXO22 supporting targeted protein degradation
Ananya A. Basu•Chenlu Zhang•Isabella A. Riha•Assa Magassa•Miguel A. Campos等 8 人
Nature Chemical Biology
2024
•2024/7/4
•00 p.1-9
Targeted protein degradation (TPD) represents a potent chemical biology paradigm that leverages the cellular degradation machinery to pharmacologically eliminate specific proteins of interest. Although multiple E3 ligases have been discovered to facilitate TPD, there exists a compelling requirement ...
ProteinsProteomics
10.1038/S41589-024-01655-9
ISSN:1552-4450
Co-occurrence of enzyme domains guides the discovery of an oxazolone synthetase
Tristan de Rond•Julia E. Asay•Bradley S. Moore
Nature Chemical Biology
2021
•2021/6/7
•00 p.1-6
Multidomain enzymes orchestrate two or more catalytic activities to carry out metabolic transformations with increased control and speed. Here, we report the design and development of a genome-mining approach for targeted discovery of biochemical transformations through the analysis of co-occurring ...
BiosynthesisComputational biology and bioinformaticsEnzymesNatural products
10.1038/S41589-021-00808-4
ISSN:1552-4450
RNAPII-dependent ATM signaling at collisions with replication forks
Elias Einig•Chao Jin•Valentina Andrioletti•Boris Macek•Nikita Popov
Nature Communications
2023
•2023/8/24
•Vol.14 No.1 p.1-17
Deregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and are thought to underlie genomic instability in tumor cells. Here we provide evidence that elonga...
Double-strand DNA breaksStalled forksTranscription
10.1038/S41467-023-40924-4
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
Restoration of energy homeostasis by SIRT6 extends healthy lifespan
A. Roichman•S. Elhanati•M. A. Aon•I. Abramovich•A. Di Francesco等 23 人
Nature Communications
2021
•2021/5/28
•Vol.12 No.1 p.1-18
Aging leads to a gradual decline in physical activity and disrupted energy homeostasis. The NAD+-dependent SIRT6 deacylase regulates aging and metabolism through mechanisms that largely remain unknown. Here, we show that SIRT6 overexpression leads to a reduction in frailty and lifespan extension in ...
AgeingMedical research
10.1038/S41467-021-23545-7
ISSN:2041-1723
The genotypes and phenotypes of missense mutations in the proline domain of the p53 protein
Hoyos David•Greenbaum Benjamin•Levine Arnold J.
Cell Death & Differentiation
2022
•2022/4/5
•00 p.1-8
The p53 protein is structurally and functionally divided into five domains. The proline-rich domain is localized at amino acids 55–100. 319 missense mutations were identified solely in the proline domain from human cancers. Six hotspot mutations were identified at amino acids 72, 73, 82, 84, 89, and...
Cancer geneticsTumour-suppressor proteins
10.1038/S41418-022-00980-7
ISSN:1350-9047
Antigen identification and high-throughput interaction mapping by reprogramming viral entry
Dobson Connor S.•Reich Anna N.•Gaglione Stephanie•Smith Blake E.•Kim Ellen J.等 12 人
Nature Methods
2022
•2022/4/8
•00 p.1-12
Deciphering immune recognition is critical for understanding a broad range of diseases and for the development of effective vaccines and immunotherapies. Efforts to do so are limited by a lack of technologies capable of simultaneously capturing the complexity of adaptive immunoreceptor repertoires a...
Adaptive immunityHigh-throughput screeningMolecular engineering
10.1038/S41592-022-01436-Z
ISSN:1548-7091
A trimodal protein language model enables advanced protein searches
Jin Su•Yan He•Shiyang You•Shiyu Jiang•Xibin Zhou等 12 人
Nature Biotechnology
2025
•2025/10/2
•00 p.1-7
ProTrek unifies protein sequence, structure and natural language function in a trimodal language model through contrastive learning, enabling comprehensive searches between any two modalities, including within modality. ProTrek surpasses current alignment tools (for example, Foldseek and MMseqs2) in...
BioinformaticsGenetic engineeringMolecular evolutionProtein databasesSequence annotation
10.1038/S41587-025-02836-0
ISSN:1087-0156
Analysing the mechanism of mitochondrial oxidation-induced cell death using a multifunctional iridium(III) photosensitiser
Chaiheon Lee•Jung Seung Nam•Chae Gyu Lee•Mingyu Park•Chang-Mo Yoo等 8 人
Nature Communications
2021
•2021/1/4
•Vol.12 No.1 p.1-11
Mitochondrial oxidation-induced cell death, a physiological process triggered by various cancer therapeutics to induce oxidative stress on tumours, has been challenging to investigate owing to the difficulties in generating mitochondria-specific oxidative stress and monitoring mitochondrial response...
Cellular imagingChemical modificationChemical toolsMitochondriaProteomics
10.1038/S41467-020-20210-3
ISSN:2041-1723
Acylspermidines are conserved mitochondrial sirtuin-dependent metabolites
Bingsen Zhang•James Mullmann•Andreas H. Ludewig•Irma R. Fernandez•Tyler R. Bales等 7 人
Nature Chemical Biology
2024
•2024/1/2
•00 p.1-11
Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent protein lysine deacylases regulating metabolism and stress responses; however, characterization of the removed acyl groups and their downstream metabolic fates remains incomplete. Here we employed untargeted comparative metabolomics to ...
Caenorhabditis elegansMetabolismMetabolomicsPost-translational modifications
10.1038/S41589-023-01511-2
ISSN:1552-4450
Molybdenum derived from nanomaterials incorporates into molybdenum enzymes and affects their activities in vivo
Mingjing Cao•Rong Cai•Lina Zhao•Mengyu Guo•Liming Wang等 18 人
Nature Nanotechnology
2021
•2021/2/18
•00 p.1-9
Many nanoscale biomaterials fail to reach the clinical trial stage due to a poor understanding of the fundamental principles of their in vivo behaviour. Here we describe the transport, transformation and bioavailability of MoS2 nanomaterials through a combination of in vivo experiments and molecular...
NanobiotechnologyNanoscale materialsNanoscience and technologyNanotoxicology
10.1038/S41565-021-00856-W
ISSN:1748-3387
Top-down mass spectrometry of native proteoforms and their complexes: a community study
Tanja Habeck•Kyle A. Brown•Benjamin Des Soye•Carter Lantz•Mowei Zhou等 22 人
Nature Methods
2024
•2024/5/14
•00 p.1-9
The combination of native electrospray ionization with top-down fragmentation in mass spectrometry (MS) allows simultaneous determination of the stoichiometry of noncovalent complexes and identification of their component proteoforms and cofactors. Although this approach is powerful, both native MS ...
Mass spectrometryProteomics
10.1038/S41592-024-02279-6
ISSN:1548-7091
Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities
Kruse Thomas•Benz Caroline•Garvanska Dimitriya H.•Lindqvist Richard•Mihalic Filip等 22 人
Nature Communications
2021
•2021/11/19
•Vol.12 No.1 p.1-13
Viral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, most current large-scale methods do not identify this important class of protein-protein interactions. Uncovering peptide mediated interactions provides both a molecular understanding of v...
Intrinsically disordered proteinsProtein–protein interaction networks
10.1038/S41467-021-26498-Z
ISSN:2041-1723
Acinetobacter baumannii OmpA-like porins: functional characterization of bacterial physiology, antibiotic-resistance, and virulence
Daniela Scribano•Elena Cheri•Arianna Pompilio•Giovanni Di Bonaventura•Manuel Belli等 11 人
Communications Biology
2024
•2024/8/6
•Vol.7 No.1 p.1-11
Acinetobacter baumannii is a critical opportunistic pathogen associated with nosocomial infections. The high rates of antibiotic-resistance acquisition make most antibiotics ineffective. Thus, new medical countermeasures are urgently needed. Outer membrane proteins (OMPs) are prime candidates for de...
BacteriologyPathogens
10.1038/S42003-024-06645-0
ISSN:2399-3642
Robust enzyme discovery and engineering with deep learning using CataPro
Zechen Wang•Dongqi Xie•Dong Wu•Xiaozhou Luo•Sheng Wang等 9 人
Nature Communications
2025
•2025/3/20
•Vol.16 No.1 p.1-16
Accurate prediction of enzyme kinetic parameters is crucial for enzyme exploration and modification. Existing models face the problem of either low accuracy or poor generalization ability due to overfitting. In this work, we first developed unbiased datasets to evaluate the actual performance of the...
EnzymesProtein designProtein function predictionsSoftware
10.1038/S41467-025-58038-4
ISSN:2041-1723
diaPASEF: parallel accumulation–serial fragmentation combined with data-independent acquisition
Florian Meier•Andreas-David Brunner•Max Frank•Annie Ha•Isabell Bludau等 14 人
Nature Methods
2020
•2020/11/30
•Vol.17 No.12 p.1229-1236
Data-independent acquisition modes isolate and concurrently fragment populations of different precursors by cycling through segments of a predefined precursor m/z range. Although these selection windows collectively cover the entire m/z range, overall, only a few per cent of all incoming ions are is...
Mass spectrometryProteome informaticsProteomics
10.1038/S41592-020-00998-0
ISSN:1548-7091
Lacking mechanistic disease definitions and corresponding association data hamper progress in network medicine and beyond
Sadegh Sepideh•Skelton James•Anastasi Elisa•Maier Andreas•Adamowicz Klaudia等 13 人
Nature Communications
2023
•2023/3/25
•Vol.14 No.1 p.1-15
A long-term objective of network medicine is to replace our current, mainly phenotype-based disease definitions by subtypes of health conditions corresponding to distinct pathomechanisms. For this, molecular and health data are modeled as networks and are mined for pathomechanisms. However, many suc...
Computer scienceData integrationData miningMolecular medicineTranslational research
10.1038/S41467-023-37349-4
ISSN:2041-1723
Structural basis for safe and efficient energy conversion in a respiratory supercomplex
Kao Wei-Chun•Ortmann de Percin Northumberland Claire•Cheng Tat Cheung•Ortiz Julio•Durand Alexandre等 10 人
Nature Communications
2022
•2022/1/27
•Vol.13 No.1 p.1-12
Proton-translocating respiratory complexes assemble into supercomplexes that are proposed to increase the efficiency of energy conversion and limit the production of harmful reactive oxygen species during aerobic cellular respiration. Cytochrome bc complexes and cytochrome aa3 oxidases are major dri...
BioenergeticsCryoelectron microscopy
10.1038/S41467-022-28179-X
ISSN:2041-1723
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
The genomic origins of the Bronze Age Tarim Basin mummies
Zhang Fan•Ning Chao•Scott Ashley•Fu Qiaomei•Bjørn Rasmus等 34 人
Nature
2021
•2021/10/27
•00 p.1-6
The identity of the earliest inhabitants of Xinjiang, in the heart of Inner Asia, and the languages that they spoke have long been debated and remain contentious1. Here we present genomic data from 5 individuals dating to around 3000–2800 bc from the Dzungarian Basin and 13 individuals dating to aro...
ArchaeologyEvolutionary geneticsPopulation genetics
10.1038/S41586-021-04052-7
ISSN:0028-0836
Exchange catalysis by tapasin exploits conserved and allele-specific features of MHC-I molecules
Huan Lan•Esam T. Abualrous•Jana Sticht•Laura Maria Arroyo Fernandez•Tamina Werk等 10 人
Nature Communications
2021
•2021/7/9
•Vol.12 No.1 p.1-13
The repertoire of peptides presented by major histocompatibility complex class I (MHC-I) molecules on the cell surface is tailored by the ER-resident peptide loading complex (PLC), which contains the exchange catalyst tapasin. Tapasin stabilizes MHC-I molecules and promotes the formation of stable p...
Antigen presentationEnzyme mechanismsMHC class INMR spectroscopy
10.1038/S41467-021-24401-4
ISSN:2041-1723
Non-classical ferroptosis inhibition by a small molecule targeting PHB2
Yang Wei•Mu Bo•You Jing•Tian Chenyu•Bin Huachao等 16 人
Nature Communications
2022
•2022/12/3
•Vol.13 No.1 p.1-16
Ferroptosis is a new type of programmed cell death characterized by iron-dependent lipid peroxidation. Ferroptosis inhibition is thought as a promising therapeutic strategy for a variety of diseases. Currently, a majority of known ferroptosis inhibitors belong to either antioxidants or iron-chelator...
Cell deathTarget identification
10.1038/S41467-022-35294-2
ISSN:2041-1723
The patterns of deleterious mutations during the domestication of soybean
Myung-Shin Kim•Roberto Lozano•Ji Hong Kim•Dong Nyuk Bae•Sang-Tae Kim等 13 人
Nature Communications
2021
•2021/1/4
•Vol.12 No.1 p.1-14
Globally, soybean is a major protein and oil crop. Enhancing our understanding of the soybean domestication and improvement process helps boost genomics-assisted breeding efforts. Here we present a genome-wide variation map of 10.6 million single-nucleotide polymorphisms and 1.4 million indels for 7...
Agricultural geneticsGenetic variation
10.1038/S41467-020-20337-3
ISSN:2041-1723
CD45 pre-exclusion from the tips of T cell microvilli prior to antigen recognition
Yunmin Jung•Lai Wen•Amnon Altman•Klaus Ley
Nature Communications
2021
•2021/6/23
•Vol.12 No.1 p.1-16
The tyrosine phosphatase CD45 is a major gatekeeper for restraining T cell activation. Its exclusion from the immunological synapse (IS) is crucial for T cell receptor (TCR) signal transduction. Here, we use expansion super-resolution microscopy to reveal that CD45 is mostly pre-excluded from the ti...
Imaging the immune systemSignal transductionSuper-resolution microscopyT cells
10.1038/S41467-021-23792-8
ISSN:2041-1723
Phosphoproteomic profiling of T cell acute lymphoblastic leukemia reveals targetable kinases and combination treatment strategies
Cordo’ Valentina•Meijer Mariska T.•Hagelaar Rico•de Goeij-de Haas Richard R.•Poort Vera M.等 13 人
Nature Communications
2022
•2022/2/25
•Vol.13 No.1 p.1-13
Protein kinase inhibitors are amongst the most successful cancer treatments, but targetable kinases activated by genomic abnormalities are rare in T cell acute lymphoblastic leukemia. Nevertheless, kinases can be activated in the absence of genetic defects. Thus, phosphoproteomics can provide inform...
Acute lymphocytic leukaemiaProteomicsTargeted therapies
10.1038/S41467-022-28682-1
ISSN:2041-1723
Phytocytokine signalling reopens stomata in plant immunity and water loss
Liu Zunyong•Hou Shuguo•Rodrigues Olivier•Wang Ping•Luo Dexian等 18 人
Nature
2022
•2022/5/4
•00 p.1-8
Stomata exert considerable effects on global carbon and water cycles by mediating gas exchange and water vapour1,2. Stomatal closure prevents water loss in response to dehydration and limits pathogen entry3,4. However, prolonged stomatal closure reduces photosynthesis and transpiration and creates a...
Plant immunityPlant signallingPlant stress responsesStomata
10.1038/S41586-022-04684-3
ISSN:0028-0836
The tepary bean genome provides insight into evolution and domestication under heat stress
Samira Mafi Moghaddam•Atena Oladzad•Chushin Koh•Larissa Ramsay•John P. Hart等 21 人
Nature Communications
2021
•2021/5/11
•Vol.12 No.1 p.1-14
Tepary bean (Phaseolus acutifolis A. Gray), native to the Sonoran Desert, is highly adapted to heat and drought. It is a sister species of common bean (Phaseolus vulgaris L.), the most important legume protein source for direct human consumption, and whose production is threatened by climate change....
Agricultural geneticsComparative genomicsGenomePlant genetics
10.1038/S41467-021-22858-X
ISSN:2041-1723
Genome dilution by cell growth drives starvation-like proteome remodeling in mammalian and yeast cells
Michael C. Lanz•Shuyuan Zhang•Matthew P. Swaffer•Inbal Ziv•Luisa Hernández Götz等 10 人
Nature Structural & Molecular Biology
2024
•2024/7/24
•00 p.1-13
Cell size is tightly controlled in healthy tissues and single-celled organisms, but it remains unclear how cell size influences physiology. Increasing cell size was recently shown to remodel the proteomes of cultured human cells, demonstrating that large and small cells of the same type can be compo...
Cell growthProteomicsSystems biology
10.1038/S41594-024-01353-Z
ISSN:1545-9993
Pick-up single-cell proteomic analysis for quantifying up to 3000 proteins in a Mammalian cell
Yu Wang•Zhi-Ying Guan•Shao-Wen Shi•Yi-Rong Jiang•Jie Zhang等 18 人
Nature Communications
2024
•2024/2/10
•Vol.15 No.1 p.1-13
The shotgun proteomic analysis is currently the most promising single-cell protein sequencing technology, however its identification level of ~1000 proteins per cell is still insufficient for practical applications. Here, we develop a pick-up single-cell proteomic analysis (PiSPA) workflow to achiev...
MicrofluidicsProteomic analysisProteomics
10.1038/S41467-024-45659-4
ISSN:2041-1723
The Scaly-foot Snail genome and implications for the origins of biomineralised armour
Jin Sun•Chong Chen•Norio Miyamoto•Runsheng Li•Julia D. Sigwart等 21 人
Nature Communications
2020
•2020/4/8
•Vol.11 No.1 p.1-12
The Scaly-foot Snail, Chrysomallon squamiferum, presents a combination of biomineralised features, reminiscent of enigmatic early fossil taxa with complex shells and sclerites such as sachtids, but in a recently-diverged living species which even has iron-infused hard parts. Thus the Scaly-foot Snai...
EvolutionGenomics
10.1038/S41467-020-15522-3
ISSN:2041-1723
PBK/TOPK mediates Ikaros, Aiolos and CTCF displacement from mitotic chromosomes and alters chromatin accessibility at selected C2H2-zinc finger protein binding sites
Andrew Dimond•Do Hyeon Gim•Elizabeth Ing-Simmons•Chad Whilding•Holger B. Kramer等 14 人
Nature Communications
2025
•2025/9/23
•Vol.16 No.1 p.1-20
PBK/TOPK is a mitotic kinase implicated in haematological and non-haematological cancers. Here we show that the key haemopoietic regulators Ikaros and Aiolos require PBK-mediated phosphorylation to dissociate from chromosomes in mitosis. Eviction of Ikaros is rapidly reversed by addition of the PBK-...
ChromatinChromosomesMitosisPhosphorylation
10.1038/S41467-025-63740-4
ISSN:2041-1723
Small-sample learning reveals propionylation in determining global protein homeostasis
Ke Shui•Chenwei Wang•Xuedi Zhang•Shanshan Ma•Qinyu Li等 16 人
Nature Communications
2023
•2023/5/17
•Vol.14 No.1 p.1-23
Proteostasis is fundamental for maintaining organismal health. However, the mechanisms underlying its dynamic regulation and how its disruptions lead to diseases are largely unclear. Here, we conduct in-depth propionylomic profiling in Drosophila, and develop a small-sample learning framework to pri...
EpigeneticsPost-translational modificationsProteomics
10.1038/S41467-023-38414-8
ISSN:2041-1723
mTORC1 controls Golgi architecture and vesicle secretion by phosphorylation of SCYL1
Kaeser-Pebernard Stéphanie•Vionnet Christine•Mari Muriel•Sankar Devanarayanan Siva•Hu Zehan等 14 人
Nature Communications
2022
•2022/8/10
•Vol.13 No.1 p.1-21
The protein kinase mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth and proliferation, supporting anabolic reactions and inhibiting catabolic pathways like autophagy. Its hyperactivation is a frequent event in cancer promoting tumor cell proliferation. Several ...
Cell signallingMembrane traffickingOrganellesProteomics
10.1038/S41467-022-32487-7
ISSN:2041-1723
Molecular basis of TASL recruitment by the peptide/histidine transporter 1, PHT1
Tânia F. Custódio•Maxime Killer•Dingquan Yu•Virginia Puente•Daniel P. Teufel等 10 人
Nature Communications
2023
•2023/9/14
•Vol.14 No.1 p.1-12
PHT1 is a histidine /oligopeptide transporter with an essential role in Toll-like receptor innate immune responses. It can act as a receptor by recruiting the adaptor protein TASL which leads to type I interferon production via IRF5. Persistent stimulation of this signalling pathway is known to be i...
Cryoelectron microscopyMolecular modellingPeptidesPermeation and transport
10.1038/S41467-023-41420-5
ISSN:2041-1723
Network medicine for disease module identification and drug repurposing with the NeDRex platform
Sadegh Sepideh•Skelton James•Anastasi Elisa•Bernett Judith•Blumenthal David B.等 16 人
Nature Communications
2021
•2021/11/25
•Vol.12 No.1 p.1-12
Traditional drug discovery faces a severe efficacy crisis. Repurposing of registered drugs provides an alternative with lower costs and faster drug development timelines. However, the data necessary for the identification of disease modules, i.e. pathways and sub-networks describing the mechanisms o...
Computational platforms and environmentsData integrationDatabasesTarget identification
10.1038/S41467-021-27138-2
ISSN:2041-1723
The Theranostic Genome
Xiaoying Xu•Pablo Jané•Vincent Taelman•Eduardo Jané•Rebecca A. Dumont等 10 人
Nature Communications
2024
•2024/12/30
•Vol.15 No.1 p.1-12
Theranostic drugs represent an emerging path to deliver on the promise of precision medicine. However, bottlenecks remain in characterizing theranostic targets, identifying theranostic lead compounds, and tailoring theranostic drugs. To overcome these bottlenecks, we present the Theranostic Genome, ...
Cancer genomicsData miningDrug developmentMachine learningMolecular medicine
10.1038/S41467-024-55291-X
ISSN:2041-1723
irCLIP-RNP and Re-CLIP reveal patterns of dynamic protein assemblies on RNA
Luca Ducoli•Brian J. Zarnegar•Douglas F. Porter•Robin M. Meyers•Weili Miao等 14 人
Nature
2025
•2025/3/26
•00 p.1-10
RNA-binding proteins (RBPs) control varied processes, including RNA splicing, stability, transport and translation1–3. Dysfunctional RNA–RBP interactions contribute to the pathogenesis of human disease1,4,5; however, characterizing the nature and dynamics of multiprotein assemblies on RNA has been c...
Biological techniquesCell biology
10.1038/S41586-025-08787-5
ISSN:0028-0836
Data-independent acquisition method for ubiquitinome analysis reveals regulation of circadian biology
Fynn M. Hansen•Maria C. Tanzer•Franziska Brüning•Isabell Bludau•Che Stafford等 9 人
Nature Communications
2021
•2021/1/11
•Vol.12 No.1 p.1-13
Protein ubiquitination is involved in virtually all cellular processes. Enrichment strategies employing antibodies targeting ubiquitin-derived diGly remnants combined with mass spectrometry (MS) have enabled investigations of ubiquitin signaling at a large scale. However, so far the power of data in...
Circadian rhythmsProteomic analysisProteomicsUbiquitylation
10.1038/S41467-020-20509-1
ISSN:2041-1723
Hierarchical TAF1-dependent co-translational assembly of the basal transcription factor TFIID
Andrea Bernardini•Pooja Mukherjee•Elisabeth Scheer•Ivanka Kamenova•Simona Antonova等 10 人
Nature Structural & Molecular Biology
2023
•2023/6/29
•00 p.1-12
Large heteromeric multiprotein complexes play pivotal roles at every step of gene expression in eukaryotic cells. Among them, the 20-subunit basal transcription factor TFIID nucleates the RNA polymerase II preinitiation complex at gene promoters. Here, by combining systematic RNA-immunoprecipitation...
DNA-binding proteinsMass spectrometryTranscriptionTranscription factorsTranslation
10.1038/S41594-023-01026-3
ISSN:1545-9993
Ribosomopathy-associated mutations cause proteotoxic stress that is alleviated by TOR inhibition
Carles Recasens-Alvarez•Cyrille Alexandre•Joanna Kirkpatrick•Hisashi Nojima•David J. Huels等 7 人
Nature Cell Biology
2021
•2021/1/25
•Vol.23 No.2 p.127-135
Ribosomes are multicomponent molecular machines that synthesize all of the proteins of living cells. Most of the genes that encode the protein components of ribosomes are therefore essential. A reduction in gene dosage is often viable albeit deleterious and is associated with human syndromes, which ...
Cell growthMechanisms of disease
10.1038/S41556-020-00626-1
ISSN:1465-7392
An antiplasmid system drives antibiotic resistance gene integration in carbapenemase-producing Escherichia coli lineages
Pengdbamba Dieudonné Zongo•Nicolas Cabanel•Guilhem Royer•Florence Depardieu•Alain Hartmann等 8 人
Nature Communications
2024
•2024/5/15
•Vol.15 No.1 p.1-15
Plasmids carrying antibiotic resistance genes (ARG) are the main mechanism of resistance dissemination in Enterobacterales. However, the fitness-resistance trade-off may result in their elimination. Chromosomal integration of ARGs preserves resistance advantage while relieving the selective pressure...
Bacterial genesBacterial geneticsClinical microbiology
10.1038/S41467-024-48219-Y
ISSN:2041-1723
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 Arabidopsis U1 snRNP regulates mRNA 3′-end processing
Anchilie F. Mangilet•Joachim Weber•Sandra Schüler•Manon Adler•Eneza Yoeli Mjema等 16 人
Nature Plants
2024
•2024/9/23
•00 p.1-18
The removal of introns by the spliceosome is a key gene regulatory mechanism in eukaryotes, with the U1 snRNP subunit playing a crucial role in the early stages of splicing. Studies in metazoans show that the U1 snRNP also conducts splicing-independent functions, but the lack of genetic tools and kn...
Gene expression analysisPlant geneticsPlant molecular biology
10.1038/S41477-024-01796-8
ISSN:2055-0278
Dense sampling of bird diversity increases power of comparative genomics
Shaohong Feng•Josefin Stiller•Yuan Deng•Joel Armstrong•Qi Fang等 150 人
Nature
2020
•2020/11/11
•Vol.587 No.7833 p.252-257
Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity1–4. Sparse taxon sampling has previously been proposed to confound phylogenetic inference5, and captures only a fraction of the genomic diversity. Here we report a substantial step towards t...
Comparative genomicsEvolutionary genetics
10.1038/S41586-020-2873-9
ISSN:0028-0836
Streamlined single-cell proteomics by an integrated microfluidic chip and data-independent acquisition mass spectrometry
Gebreyesus Sofani Tafesse•Siyal Asad Ali•Kitata Reta Birhanu•Chen Eric Sheng-Wen•Enkhbayar Bayarmaa等 9 人
Nature Communications
2022
•2022/1/10
•Vol.13 No.1 p.1-13
Single-cell proteomics can reveal cellular phenotypic heterogeneity and cell-specific functional networks underlying biological processes. Here, we present a streamlined workflow combining microfluidic chips for all-in-one proteomic sample preparation and data-independent acquisition (DIA) mass spec...
Lab-on-a-chipMass spectrometryProteomeProteomics
10.1038/S41467-021-27778-4
ISSN:2041-1723
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
Malaria parasite heme biosynthesis promotes and griseofulvin protects against cerebral malaria in mice
Chandana Manjunatha•Anand Aditya•Ghosh Sourav•Das Rahul•Beura Subhashree等 9 人
Nature Communications
2022
•2022/7/12
•Vol.13 No.1 p.1-22
Heme-biosynthetic pathway of malaria parasite is dispensable for asexual stages, but essential for mosquito and liver stages. Despite having backup mechanisms to acquire hemoglobin-heme, pathway intermediates and/or enzymes from the host, asexual parasites express heme pathway enzymes and synthesize...
MalariaMechanisms of diseaseParasite biology
10.1038/S41467-022-31431-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
PEX39 facilitates the peroxisomal import of PTS2-containing proteins
Walter W. Chen•Tony A. Rodrigues•Daniel Wendscheck•Ana G. Pedrosa•Chendong Yang等 26 人
Nature Cell Biology
2025
•2025/7/30
•00 p.1-16
Peroxisomes are metabolic organelles essential for human health. Defects in peroxisomal biogenesis proteins (also known as peroxins (PEXs)) cause devastating disease. PEX7 binds proteins containing a type 2 peroxisomal targeting signal (PTS2) to enable their import from the cytosol into peroxisomes,...
PeroxisomesProtein–protein interaction networksProtein translocationProteins
10.1038/S41556-025-01711-Z
ISSN:1465-7392
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
Outlining cardiac ion channel protein interactors and their signature in the human electrocardiogram
Svetlana Maurya•Robert W. Mills•Konstantin Kahnert•David Y. Chiang•Giorgia Bertoli等 13 人
Nature Cardiovascular Research
2023
•2023/7/13
•Vol.2 No.7 p.673-692
Protein–protein interactions are essential for normal cellular processes and signaling events. Defining these interaction networks is therefore crucial for understanding complex cellular functions and interpretation of disease-associated gene variants. We need to build a comprehensive picture of the...
Cardiovascular biologyData integrationProtein analysisProteomics
10.1038/S44161-023-00294-Y
ISSN:2731-0590
Platypus and echidna genomes reveal mammalian biology and evolution
Yang Zhou•Linda Shearwin-Whyatt•Jing Li•Zhenzhen Song•Takashi Hayakawa等 42 人
Nature
2021
•2021/1/6
•00 p.1-7
Egg-laying mammals (monotremes) are the only extant mammalian outgroup to therians (marsupial and eutherian animals) and provide key insights into mammalian evolution1,2. Here we generate and analyse reference genomes of the platypus (Ornithorhynchus anatinus) and echidna (Tachyglossus aculeatus), w...
Comparative genomicsEvolutionary genetics
10.1038/S41586-020-03039-0
ISSN:0028-0836
CatPred: a comprehensive framework for deep learning in vitro enzyme kinetic parameters
Veda Sheersh Boorla•Costas D. Maranas
Nature Communications
2025
•2025/2/28
•Vol.16 No.1 p.1-17
Estimation of enzymatic activities still heavily relies on experimental assays, which can be cost and time-intensive. We present CatPred, a deep learning framework for predicting in vitro enzyme kinetic parameters, including turnover numbers (kcat), Michaelis constants (Km), and inhibition constants...
EnzymesKineticsMachine learningProtein function predictions
10.1038/S41467-025-57215-9
ISSN:2041-1723
Inhibition of CBP synergizes with the RNA-dependent mechanisms of Azacitidine by limiting protein synthesis
Diesch Jeannine•Le Pannérer Marguerite-Marie•Winkler René•Casquero Raquel•Muhar Matthias等 18 人
Nature Communications
2021
•2021/10/18
•Vol.12 No.1 p.1-13
The nucleotide analogue azacitidine (AZA) is currently the best treatment option for patients with high-risk myelodysplastic syndromes (MDS). However, only half of treated patients respond and of these almost all eventually relapse. New treatment options are urgently needed to improve the clinical m...
Acute myeloid leukaemiaMyelodysplastic syndrome
10.1038/S41467-021-26258-Z
ISSN:2041-1723
Cell division in the archaeon Haloferax volcanii relies on two FtsZ proteins with distinct functions in division ring assembly and constriction
Yan Liao•Solenne Ithurbide•Christian Evenhuis•Jan Löwe•Iain G. Duggin
Nature Microbiology
2021
•2021/4/26
•Vol.6 No.5 p.594-605
In bacteria, the tubulin homologue FtsZ assembles a cytokinetic ring, termed the Z ring, and plays a key role in the machinery that constricts to divide the cells. Many archaea encode two FtsZ proteins from distinct families, FtsZ1 and FtsZ2, with previously unclear functions. Here, we show that Hal...
Archaeal biologyCellular microbiology
10.1038/S41564-021-00894-Z
ISSN:2058-5276
Protein sequence modelling with Bayesian flow networks
Timothy Atkinson•Thomas D. Barrett•Scott Cameron•Bora Guloglu•Matthew Greenig等 10 人
Nature Communications
2025
•2025/4/3
•Vol.16 No.1 p.1-14
Exploring the vast and largely uncharted territory of amino acid sequences is crucial for understanding complex protein functions and the engineering of novel therapeutic proteins. Whilst generative machine learning has advanced protein sequence modelling, no existing approach is proficient in both ...
Computational modelsMachine learningProtein design
10.1038/S41467-025-58250-2
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
Antibody toolkit reveals N-terminally ubiquitinated substrates of UBE2W
Davies Christopher W.•Vidal Simon E.•Phu Lilian•Sudhamsu Jawahar•Hinkle Trent B.等 16 人
Nature Communications
2021
•2021/7/29
•Vol.12 No.1 p.1-19
The ubiquitin conjugating enzyme UBE2W catalyzes non-canonical ubiquitination on the N-termini of proteins, although its substrate repertoire remains unclear. To identify endogenous N-terminally-ubiquitinated substrates, we discover four monoclonal antibodies that selectively recognize tryptic pepti...
Antibody generationProteomicsUbiquitylationX-ray crystallography
10.1038/S41467-021-24669-6
ISSN:2041-1723
Delineating cysteine-reactive compound modulation of cellular proteostasis processes
Ashley R. Julio•Flowreen Shikwana•Cindy Truong•Nikolas R. Burton•Emil R. Dominguez等 8 人
Nature Chemical Biology
2024
•2024/10/24
•00 p.1-13
Covalent modulators and covalent degrader molecules have emerged as drug modalities with tremendous therapeutic potential. Toward realizing this potential, mass spectrometry-based chemoproteomic screens have generated proteome-wide maps of potential druggable cysteine residues. However, beyond these...
Protein aggregationProteomicsSmall moleculesTarget identification
10.1038/S41589-024-01760-9
ISSN:1552-4450
The SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation
Johannes Benedum•Vedran Franke•Lisa-Marie Appel•Lena Walch•Melania Bruno等 14 人
Nature Communications
2023
•2023/11/30
•Vol.14 No.1 p.1-20
Transcription is regulated by a multitude of activators and repressors, which bind to the RNA polymerase II (Pol II) machinery and modulate its progression. Death-inducer obliterator 3 (DIDO3) and PHD finger protein 3 (PHF3) are paralogue proteins that regulate transcription elongation by docking on...
Gene expressionNeural stem cellsProtein–protein interaction networksTranscription
10.1038/S41467-023-43724-Y
ISSN:2041-1723
Multi-proteomic profiling of the varicella-zoster virus–host interface reveals host susceptibilities to severe infection
Virginie Girault•Alexey Stukalov•Madalina Elena Carter-Timofte•Jonny Hertzog•Melissa Verin等 18 人
Nature Microbiology
2025
•2025/7/30
•Vol.10 No.8 p.2048-2072
Varicella-zoster virus (VZV) infects most humans and causes chickenpox, shingles and central nervous system pathologies. The molecular basis for these phenotypes remains elusive. Here we conducted a multi-proteomic survey on 64 individual VZV proteins and infection-induced perturbations in a neurona...
InfectionInfectious diseasesSystems biologyVirology
10.1038/S41564-025-02068-7
ISSN:2058-5276
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
Cryo-EM structure and molecular mechanism of abscisic acid transporter ABCG25
Xiaowei Huang•Xue Zhang•Ning An•Minhua Zhang•Miaolian Ma等 10 人
Nature Plants
2023
•2023/9/4
•00 p.1-11
Abscisic acid (ABA) is one of the plant hormones that regulate various physiological processes, including stomatal closure, seed germination and development. ABA is synthesized mainly in vascular tissues and transported to distal sites to exert its physiological functions. Many ABA transporters have...
AbioticCryoelectron microscopyPlant hormones
10.1038/S41477-023-01509-7
ISSN:2055-0278
Dual DNA and protein tagging of open chromatin unveils dynamics of epigenomic landscapes in leukemia
Jonathan D. Lee•Joao A. Paulo•Ryan R. Posey•Vera Mugoni•Nikki R. Kong等 12 人
Nature Methods
2021
•2021/3/1
•Vol.18 No.3 p.293-302
The architecture of chromatin regulates eukaryotic cell states by controlling transcription factor access to sites of gene regulation. Here we describe a dual transposase–peroxidase approach, integrative DNA and protein tagging (iDAPT), which detects both DNA (iDAPT-seq) and protein (iDAPT-MS) assoc...
BiochemistryEpigenetics analysisFunctional genomicsProteomics
10.1038/S41592-021-01077-8
ISSN:1548-7091
Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci
Yin Xianyong•Chan Lap Sum•Bose Debraj•Jackson Anne U.•VandeHaar Peter等 37 人
Nature Communications
2022
•2022/3/28
•Vol.13 No.1 p.1-14
Few studies have explored the impact of rare variants (minor allele frequency < 1%) on highly heritable plasma metabolites identified in metabolomic screens. The Finnish population provides an ideal opportunity for such explorations, given the multiple bottlenecks and expansions that have shaped ...
BiomarkersGenome-wide association studiesQuantitative trait loci
10.1038/S41467-022-29143-5
ISSN:2041-1723
Cancer genomes tolerate deleterious coding mutations through somatic copy number amplifications of wild-type regions
Fabio Alfieri•Giulio Caravagna•Martin H. Schaefer
Nature Communications
2023
•2023/6/16
•Vol.14 No.1 p.1-13
Cancers evolve under the accumulation of thousands of somatic mutations and chromosomal aberrations. While most coding mutations are deleterious, almost all protein-coding genes lack detectable signals of negative selection. This raises the question of how tumors tolerate such large amounts of delet...
Cancer genomicsComputational biology and bioinformaticsEvolutionary theoryGene amplificationTumour heterogeneity
10.1038/S41467-023-39313-8
ISSN:2041-1723
ATP synthase evolution on a cross-braced dated tree of life
Tara A. Mahendrarajah•Edmund R. R. Moody•Dominik Schrempf•Lénárd L. Szánthó•Nina Dombrowski等 11 人
Nature Communications
2023
•2023/11/17
•Vol.14 No.1 p.1-18
The timing of early cellular evolution, from the divergence of Archaea and Bacteria to the origin of eukaryotes, is poorly constrained. The ATP synthase complex is thought to have originated prior to the Last Universal Common Ancestor (LUCA) and analyses of ATP synthase genes, together with ribosome...
Archaeal evolutionBacterial evolutionMolecular evolutionPhylogenetics
10.1038/S41467-023-42924-W
ISSN:2041-1723
Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation
Jin Meihua•Shiwaku Hiroki•Tanaka Hikari•Obita Takayuki•Ohuchi Sakurako等 13 人
Nature Communications
2021
•2021/11/15
•Vol.12 No.1 p.1-22
Brain inflammation generally accompanies and accelerates neurodegeneration. Here we report a microglial mechanism in which polyglutamine binding protein 1 (PQBP1) senses extrinsic tau 3R/4R proteins by direct interaction and triggers an innate immune response by activating a cyclic GMP-AMP synthase ...
Alzheimer's diseaseInnate immunityNeurodegenerationNeuroimmunology
10.1038/S41467-021-26851-2
ISSN:2041-1723
Mutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome
Valeria Capaci•Lorenzo Bascetta•Marco Fantuz•Galina V. Beznoussenko•Roberta Sommaggio等 24 人
Nature Communications
2020
•2020/8/7
•Vol.11 No.1 p.1-19
TP53 missense mutations leading to the expression of mutant p53 oncoproteins are frequent driver events during tumorigenesis. p53 mutants promote tumor growth, metastasis and chemoresistance by affecting fundamental cellular pathways and functions. Here, we demonstrate that p53 mutants modify struct...
Cancer microenvironmentGolgiMetastasisOncogenesSuper-resolution microscopy
10.1038/S41467-020-17596-5
ISSN:2041-1723
Cytidine diphosphate diacylglycerol synthase 2 is a synthetic lethal target in mesenchymal-like cancers
Tim Arnoldus•Alex van Vliet•Onno B. Bleijerveld•Adriaan F. H. de Groot•Qinglin Piao等 19 人
Nature Genetics
2025
•2025/7/4
•Vol.57 No.7 p.1659-1671
Synthetic lethal interactions (SLIs) based on genomic alterations in cancer have been therapeutically explored. We investigated the SLI space as a function of differential RNA expression in cancer and normal tissue. Computational analyses of functional genomic and gene expression resources uncovered...
Cancer therapyChemical biologyData miningFunctional genomicsGene expression
10.1038/S41588-025-02221-2
ISSN:1061-4036
Deep learning-based kcat prediction enables improved enzyme-constrained model reconstruction
Li Feiran•Yuan Le•Lu Hongzhong•Li Gang•Chen Yu等 8 人
Nature Catalysis
2022
•2022/6/16
•00 p.1-11
Enzyme turnover numbers (kcat) are key to understanding cellular metabolism, proteome allocation and physiological diversity, but experimentally measured kcat data are sparse and noisy. Here we provide a deep learning approach (DLKcat) for high-throughput kcat prediction for metabolic enzymes from a...
Computational biology and bioinformaticsEnzymesSystems biology
10.1038/S41929-022-00798-Z
ISSN:2520-1158
Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction
Zijlmans Dick W.•Talon Irene•Verhelst Sigrid•Bendall Adam•Van Nerum Karlien等 37 人
Nature Cell Biology
2022
•2022/6/13
•Vol.24 No.6 p.858-871
Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here we define the chromatin-associated proteome, histone post-translational modificatio...
ChromatinEpigeneticsPluripotencyTotipotent stem cells
10.1038/S41556-022-00932-W
ISSN:1465-7392
Influence of different sample preparation approaches on proteoform identification by top-down proteomics
Philipp T. Kaulich•Kyowon Jeong•Oliver Kohlbacher•Andreas Tholey
Nature Methods
2024
•2024/10/22
•00 p.1-11
Top-down proteomics using mass spectrometry facilitates the identification of intact proteoforms, that is, all molecular forms of proteins. Multiple past advances have lead to the development of numerous sample preparation workflows. Here we systematically investigated the influence of different sam...
Mass spectrometryProteomic analysisProteomics
10.1038/S41592-024-02481-6
ISSN:1548-7091
Selective regulation of macrophage lipid metabolism via nanomaterials’ surface chemistry
Junguang Wu•Xuan Bai•Liang Yan•Didar Baimanov•Yalin Cong等 19 人
Nature Communications
2024
•2024/9/27
•Vol.15 No.1 p.1-18
Understanding the interface between nanomaterials and lipoproteins is crucial for gaining insights into their impact on lipoprotein structure and lipid metabolism. Here, we use graphene oxide (GOs) nanosheets as a controlled carbon nanomaterial model to study how surface properties influence lipopro...
Biomaterials – proteinsEnvironmental, health and safety issuesMethods of toxicology studies
10.1038/S41467-024-52609-7
ISSN:2041-1723
Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix
Kay Emily J.•Paterson Karla•Riera-Domingo Carla•Sumpton David•Däbritz J. Henry M.等 29 人
Nature Metabolism
2022
•2022/6/27
•Vol.4 No.6 p.693-710
Elevated production of collagen-rich extracellular matrix is a hallmark of cancer-associated fibroblasts (CAFs) and a central driver of cancer aggressiveness. Here we find that proline, a highly abundant amino acid in collagen proteins, is newly synthesized from glutamine in CAFs to make tumour coll...
Cancer metabolismCancer microenvironmentMetabolism
10.1038/S42255-022-00582-0
ISSN:2522-5812
Strain-release alkylation of Asp12 enables mutant selective targeting of K-Ras-G12D
Qinheng Zheng•Ziyang Zhang•Keelan Z. Guiley•Kevan M. Shokat
Nature Chemical Biology
2024
•2024/3/5
•00 p.1-9
K-Ras is the most commonly mutated oncogene in human cancer. The recently approved non-small cell lung cancer drugs sotorasib and adagrasib covalently capture an acquired cysteine in K-Ras-G12C mutation and lock it in a signaling-incompetent state. However, covalent inhibition of G12D, the most freq...
Cancer therapyCell signallingMedicinal chemistrySmall molecules
10.1038/S41589-024-01565-W
ISSN:1552-4450
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
Covariation MS uncovers a protein that controls cysteine catabolism
Haopeng Xiao•Martha Ordonez•Emma C. Fink•Taylor A. Covington•Hilina B. Woldemichael等 31 人
Nature
2025
•2025/9/17
•00 p.1-9
The regulation of metabolic processes by proteins is fundamental to biology and yet is incompletely understood. Here we develop a mass spectrometry (MS)-based approach that leverages genetic diversity to nominate functional relationships between 285 metabolites and 11,868 proteins in living tis...
Biological techniquesCell biology
10.1038/S41586-025-09535-5
ISSN:0028-0836
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives chronic kidney disease progression in male mice
Yang Yunwen•Liu Suwen•Wang Peipei•Ouyang Jing•Zhou Ning等 9 人
Nature Communications
2023
•2023/3/11
•Vol.14 No.1 p.1-17
Kidney injury initiates epithelial dedifferentiation and myofibroblast activation during the progression of chronic kidney disease. Herein, we find that the expression of DNA-PKcs is significantly increased in the kidney tissues of both chronic kidney disease patients and male mice induced by unilat...
Chronic kidney diseaseMolecular biology
10.1038/S41467-023-37043-5
ISSN:2041-1723
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
A chromosomal-scale genome assembly of modern cultivated hybrid sugarcane provides insights into origination and evolution
Yixue Bao•Qing Zhang•Jiangfeng Huang•Shengcheng Zhang•Wei Yao等 25 人
Nature Communications
2024
•2024/4/8
•Vol.15 No.1 p.1-14
Sugarcane is a vital crop with significant economic and industrial value. However, the cultivated sugarcane’s ultra-complex genome still needs to be resolved due to its high ploidy and extensive recombination between the two subgenomes. Here, we generate a chromosomal-scale, haplotype-resolved genom...
Agricultural geneticsComparative genomicsEvolutionary geneticsPlant breeding
10.1038/S41467-024-47390-6
ISSN:2041-1723
Systematic analysis and prediction of genes associated with monogenic disorders on human chromosome X
Leitão Elsa•Schröder Christopher•Parenti Ilaria•Dalle Carine•Rastetter Agnès等 37 人
Nature Communications
2022
•2022/11/2
•Vol.13 No.1 p.1-17
Disease gene discovery on chromosome (chr) X is challenging owing to its unique modes of inheritance. We undertook a systematic analysis of human chrX genes. We observe a higher proportion of disorder-associated genes and an enrichment of genes involved in cognition, language, and seizures on chrX c...
GeneticsNeurodevelopmental disorders
10.1038/S41467-022-34264-Y
ISSN:2041-1723
In situ analysis of nanoparticle soft corona and dynamic evolution
Baimanov Didar•Wang Jing•Zhang Jun•Liu Ke•Cong Yalin等 14 人
Nature Communications
2022
•2022/9/14
•Vol.13 No.1 p.1-14
How soft corona, the protein corona’s outer layer, contributes to biological identity of nanomaterials is largely because capturing protein composition of the soft corona in situ remains challenging. We herein develop an in situ Fishing method that can monitor the dynamic formation of protein corona...
Cell–particle interactionsNanoparticlesProteomics
10.1038/S41467-022-33044-Y
ISSN:2041-1723
Multimodal cell maps as a foundation for structural and functional genomics
Leah V. Schaffer•Mengzhou Hu•Gege Qian•Kyung-Mee Moon•Abantika Pal等 34 人
Nature
2025
•2025/4/9
•00 p.1-10
Human cells consist of a complex hierarchy of components, many of which remain unexplored1,2. Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells. Self-...
Data integrationMachine learningNetwork topologyProteome informatics
10.1038/S41586-025-08878-3
ISSN:0028-0836
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
A natural allele of proteasome maturation factor improves rice resistance to multiple pathogens
Hu Xiao-Hong•Shen Shuai•Wu Jin-Long•Liu Jie•Wang He等 27 人
Nature Plants
2023
•2023/1/16
•Vol.9 No.2 p.228-237
Crops with broad-spectrum resistance loci are highly desirable in agricultural production because these loci often confer resistance to most races of a pathogen or multiple pathogen species. Here we discover a natural allele of proteasome maturation factor in rice, UMP1R2115, that confers broad-spec...
Natural variation in plantsPlant immunityProtein sequencingRNA sequencing
10.1038/S41477-022-01327-3
ISSN:2055-0278
IceR improves proteome coverage and data completeness in global and single-cell proteomics
Kalxdorf Mathias•Müller Torsten•Stegle Oliver•Krijgsveld Jeroen
Nature Communications
2021
•2021/8/9
•Vol.12 No.1 p.1-15
Label-free proteomics by data-dependent acquisition enables the unbiased quantification of thousands of proteins, however it notoriously suffers from high rates of missing values, thus prohibiting consistent protein quantification across large sample cohorts. To solve this, we here present IceR (Ion...
Mass spectrometryProteome informaticsProteomics
10.1038/S41467-021-25077-6
ISSN:2041-1723
An anti-influenza A virus microbial metabolite acts by degrading viral endonuclease PA
Zhao Jianyuan•Wang Jing•Pang Xu•Liu Zhenlong•Li Quanjie等 19 人
Nature Communications
2022
•2022/4/19
•Vol.13 No.1 p.1-11
The emergence of new highly pathogenic and drug-resistant influenza strains urges the development of novel therapeutics for influenza A virus (IAV). Here, we report the discovery of an anti-IAV microbial metabolite called APL-16-5 that was originally isolated from the plant endophytic fungus Aspergi...
Antiviral agentsInfluenza virusPost-translational modificationsTarget identification
10.1038/S41467-022-29690-X
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
Photosensitizer proximity labeling captures the lipid and protein interactomes
Andrew P. Becker•Elijah Biletch•John Paul Kennelly•Soon-Gook Hong•Ashley R. Julio等 17 人
Nature Chemical Biology
2026
•2026/2/6
•00 p.1-11
The physical properties of cellular membranes are influenced by protein and lipid interactions. In situ proximity labeling interactomic methods are well suited to characterize these dynamic and often fleeting interactions. Yet, available methods require distinct chemistries for proteins and lipids. ...
Protein–protein interaction networksProteomicsSterols
10.1038/S41589-026-02140-1
ISSN:1552-4450
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
Enamel proteins from six Homo erectus specimens across China
Qiaomei Fu•Zhongyou Wu•E. Andrew Bennett•Song Xing•Qiang Ji等 12 人
Nature
2026
•2026/5/13
•00 p.1-7
Homo erectus remains have been found in Africa, Eurasia and Southeast Asia1–3, dating back around two million years; however, owing to their age and state of preservation, obtaining informative molecular data from them has proved challenging. Here we successfully extracted and analysed ancient ename...
PalaeontologyProteomics
10.1038/S41586-026-10478-8
ISSN:0028-0836
A chromosome-level Camptotheca acuminata genome assembly provides insights into the evolutionary origin of camptothecin biosynthesis
Minghui Kang•Rao Fu•Pingyu Zhang•Shangling Lou•Xuchen Yang等 10 人
Nature Communications
2021
•2021/6/10
•Vol.12 No.1 p.1-12
Camptothecin and its derivatives are widely used for treating malignant tumors. Previous studies revealed only a limited number of candidate genes for camptothecin biosynthesis in Camptotheca acuminata, and it is still poorly understood how its biosynthesis of camptothecin has evolved. Here, we repo...
Comparative genomicsPlant evolutionSecondary metabolism
10.1038/S41467-021-23872-9
ISSN:2041-1723
Cell surface thermal proteome profiling tracks perturbations and drug targets on the plasma membrane
Mathias Kalxdorf•Ina Günthner•Isabelle Becher•Nils Kurzawa•Sascha Knecht等 8 人
Nature Methods
2021
•2021/1/4
•Vol.18 No.1 p.84-91
Numerous drugs and endogenous ligands bind to cell surface receptors leading to modulation of downstream signaling cascades and frequently to adaptation of the plasma membrane proteome. In-depth analysis of dynamic processes at the cell surface is challenging due to biochemical properties and low ab...
Drug discoveryKinasesMass spectrometryProtein–protein interaction networksProteomics
10.1038/S41592-020-01022-1
ISSN:1548-7091
Mechanistic understanding of human SLFN11
Metzner Felix J.•Wenzl Simon J.•Kugler Michael•Krebs Stefan•Hopfner Karl-Peter等 6 人
Nature Communications
2022
•2022/9/17
•Vol.13 No.1 p.1-10
Schlafen 11 (SLFN11) is an interferon-inducible antiviral restriction factor with tRNA endoribonuclease and DNA binding functions. It is recruited to stalled replication forks in response to replication stress and inhibits replication of certain viruses such as the human immunodeficiency virus 1 (HI...
Cryoelectron microscopyEnzyme mechanismsHIV infectionsTumour biomarkers
10.1038/S41467-022-33123-0
ISSN:2041-1723
Lumenal Galectin-9-Lamp2 interaction regulates lysosome and autophagy to prevent pathogenesis in the intestine and pancreas
Janaki N. Sudhakar•Hsueh-Han Lu•Hung-Yu Chiang•Ching-Shu Suen•Ming-Jing Hwang等 11 人
Nature Communications
2020
•2020/8/27
•Vol.11 No.1 p.1-17
Intracellular galectins are carbohydrate-binding proteins capable of sensing and repairing damaged lysosomes. As in the physiological conditions glycosylated moieties are mostly in the lysosomal lumen but not cytosol, it is unclear whether galectins reside in lysosomes, bind to glycosylated proteins...
Cell biologyDiseasesGastroenterologyImmunologyPathogenesis
10.1038/S41467-020-18102-7
ISSN:2041-1723
A class I PI3K signalling network regulates primary cilia disassembly in normal physiology and disease
Sarah E. Conduit•Wayne Pearce•Amandeep Bhamra•Benoit Bilanges•Laura Bozal-Basterra等 17 人
Nature Communications
2024
•2024/8/21
•Vol.15 No.1 p.1-21
Primary cilia are antenna-like organelles which sense extracellular cues and act as signalling hubs. Cilia dysfunction causes a heterogeneous group of disorders known as ciliopathy syndromes affecting most organs. Cilia disassembly, the process by which cells lose their cilium, is poorly understood ...
CiliogenesisLipid signallingMechanisms of disease
10.1038/S41467-024-51354-1
ISSN:2041-1723
Cell surface-localized CsgF condensate is a gatekeeper in bacterial curli subunit secretion
Swasthi Hema M.•Basalla Joseph L.•Dudley Claire E.•Vecchiarelli Anthony G.•Chapman Matthew R.
Nature Communications
2023
•2023/4/26
•Vol.14 No.1 p.1-13
Curli are functional amyloids present on the outer membrane of E. coli. CsgF is required for the proper assembly of curli. Here, we found that the CsgF phase separates in vitro and that the ability of CsgF variants to phase-separate is tightly correlated with CsgF function during curli biogenesis. S...
BiofilmsProtein aggregation
10.1038/S41467-023-38089-1
ISSN:2041-1723
An accessible workflow for high-sensitivity proteomics using parallel accumulation–serial fragmentation (PASEF)
Patricia Skowronek•Georg Wallmann•Maria Wahle•Sander Willems•Matthias Mann
Nature Protocols
2025
•2025/1/17
•00 p.1-30
Deep and accurate proteome analysis is crucial for understanding cellular processes and disease mechanisms; however, it is challenging to implement in routine settings. In this protocol, we combine a robust chromatographic platform with a high-performance mass spectrometric setup to enable routine y...
Mass spectrometryProteomics
10.1038/S41596-024-01104-W
ISSN:1754-2189
G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis
Wenmeng Wang•Dangdang Li•Qingqing Xu•Jiahui Cheng•Zhiwei Yu等 12 人
Nature Communications
2024
•2024/2/5
•Vol.15 No.1 p.1-17
G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 o...
Intrinsically disordered proteinsOncogenesTranscriptional regulatory elements
10.1038/S41467-024-45353-5
ISSN:2041-1723
Monitoring Fe–S cluster occupancy across the E. coli proteome using chemoproteomics
Bak Daniel W.•Weerapana Eranthie
Nature Chemical Biology
2023
•2023/1/12
•Vol.19 No.3 p.356-366
Iron–sulfur (Fe–S) clusters are ubiquitous metallocofactors involved in redox chemistry, radical generation and gene regulation. Common methods to monitor Fe–S clusters include spectroscopic analysis of purified proteins and autoradiographic visualization of radiolabeled iron distribution in proteom...
MetalloproteinsMetalsModel prokaryotesProteomics
10.1038/S41589-022-01227-9
ISSN:1552-4450
Annotating protein functions via fusing multiple biological modalities
Wenjian Ma•Xiangpeng Bi•Huasen Jiang•Zhiqiang Wei•Shugang Zhang
Communications Biology
2024
•2024/12/27
•Vol.7 No.1 p.1-13
Understanding the function of proteins is of great significance for revealing disease pathogenesis and discovering new targets. Benefiting from the explosive growth of the protein universal, deep learning has been applied to accelerate the protein annotation cycle from different biological modalitie...
Machine learningProtein function predictions
10.1038/S42003-024-07411-Y
ISSN:2399-3642
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
Resolving the metabolism of monolignols and other lignin-related aromatic compounds in Xanthomonas citri
Damaris B. Martim•Anna J. V. C. Brilhante•Augusto R. Lima•Douglas A. A. Paixão•Joaquim Martins-Junior等 15 人
Nature Communications
2024
•2024/9/12
•Vol.15 No.1 p.1-17
Lignin, a major plant cell wall component, has an important role in plant-defense mechanisms against pathogens and is a promising renewable carbon source to produce bio-based chemicals. However, our understanding of microbial metabolism is incomplete regarding certain lignin-related compounds like p...
BiocatalysisEnvironmental microbiologyMetabolic pathways
10.1038/S41467-024-52367-6
ISSN:2041-1723
Reversible conjugation of a CBASS nucleotide cyclase regulates bacterial immune response to phage infection
Larissa Krüger•Laura Gaskell-Mew•Shirley Graham•Sally Shirran•Robert Hertel等 6 人
Nature Microbiology
2024
•2024/4/8
•00 p.1-14
Prokaryotic antiviral defence systems are frequently toxic for host cells and stringent regulation is required to ensure survival and fitness. These systems must be readily available in case of infection but tightly controlled to prevent activation of an unnecessary cellular response. Here we invest...
DNA restriction-modification enzymesPhage biologyUbiquitylation
10.1038/S41564-024-01670-5
ISSN:2058-5276
Photoproximity labeling of endogenous receptors in the live mouse brain in minutes
Mikiko Takato•Seiji Sakamoto•Hiroshi Nonaka•Fátima Yuri Tanimura Valor•Tomonori Tamura等 6 人
Nature Chemical Biology
2024
•2024/8/1
•00 p.1-11
Understanding how protein–protein interaction networks in the brain give rise to cognitive functions necessitates their characterization in live animals. However, tools available for this purpose require potentially disruptive genetic modifications and lack the temporal resolution necessary to track...
Chemical toolsMolecular neuroscienceProtein–protein interaction networks
10.1038/S41589-024-01692-4
ISSN:1552-4450
VCP/p97-associated proteins are binders and debranching enzymes of K48–K63-branched ubiquitin chains
Sven M. Lange•Matthew R. McFarland•Frederic Lamoliatte•Thomas Carroll•Logesvaran Krshnan等 15 人
Nature Structural & Molecular Biology
2024
•2024/7/8
•00 p.1-16
Branched ubiquitin (Ub) chains constitute a sizable fraction of Ub polymers in human cells. Despite their abundance, our understanding of branched Ub function in cell signaling has been stunted by the absence of accessible methods and tools. Here we identify cellular branched-chain-specific binding ...
Cell signallingDeubiquitylating enzymesStructural biologyUbiquitylationX-ray crystallography
10.1038/S41594-024-01354-Y
ISSN:1545-9993
Data integration across conditions improves turnover number estimates and metabolic predictions
Wendering Philipp•Arend Marius•Razaghi-Moghadam Zahra•Nikoloski Zoran
Nature Communications
2023
•2023/3/17
•Vol.14 No.1 p.1-12
Turnover numbers characterize a key property of enzymes, and their usage in constraint-based metabolic modeling is expected to increase the prediction accuracy of diverse cellular phenotypes. In vivo turnover numbers can be obtained by integrating reaction rate and enzyme abundance measurements from...
Biochemical reaction networksBioinformaticsComputational modelsMetabolic engineering
10.1038/S41467-023-37151-2
ISSN:2041-1723
Phosphorylation-driven epichaperome assembly is a regulator of cellular adaptability and proliferation
Tanaya Roychowdhury•Seth W. McNutt•Chiranjeevi Pasala•Hieu T. Nguyen•Daniel T. Thornton等 32 人
Nature Communications
2024
•2024/10/16
•Vol.15 No.1 p.1-28
The intricate network of protein-chaperone interactions is crucial for maintaining cellular function. Recent discoveries have unveiled the existence of specialized chaperone assemblies, known as epichaperomes, which serve as scaffolding platforms that orchestrate the reconfiguration of protein-prote...
ChaperonesMass spectrometryMechanisms of diseasePhosphorylation
10.1038/S41467-024-53178-5
ISSN:2041-1723
Network-based machine learning in colorectal and bladder organoid models predicts anti-cancer drug efficacy in patients
JungHo Kong•Heetak Lee•Donghyo Kim•Seong Kyu Han•Doyeon Ha等 7 人
Nature Communications
2020
•2020/10/30
•Vol.11 No.1 p.1-13
Cancer patient classification using predictive biomarkers for anti-cancer drug responses is essential for improving therapeutic outcomes. However, current machine-learning-based predictions of drug response often fail to identify robust translational biomarkers from preclinical models. Here, we pres...
Drug developmentGene regulatory networksMachine learning
10.1038/S41467-020-19313-8
ISSN:2041-1723
Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides
Yang Xinbo•Garner Lee I.•Zvyagin Ivan V.•Paley Michael A.•Komech Ekaterina A.等 19 人
Nature
2022
•2022/12/7
•Vol.612 No.7941 p.771-777
Human leucocyte antigen B*27 (HLA-B*27) is strongly associated with inflammatory diseases of the spine and pelvis (for example, ankylosing spondylitis (AS)) and the eye (that is, acute anterior uveitis (AAU))1. How HLA-B*27 facilitates disease remains unknown, but one possible mechanism could involv...
AutoimmunitySpondyloarthritis
10.1038/S41586-022-05501-7
ISSN:0028-0836
System-wide analysis of RNA and protein subcellular localization dynamics
Eneko Villanueva•Tom Smith•Mariavittoria Pizzinga•Mohamed Elzek•Rayner M. L. Queiroz等 12 人
Nature Methods
2023
•2023/11/30
•00 p.1-12
Although the subcellular dynamics of RNA and proteins are key determinants of cell homeostasis, their characterization is still challenging. Here we present an integrative framework to simultaneously interrogate the dynamics of the transcriptome and proteome at subcellular resolution by combining tw...
Cell biologyProteomicsSequencing
10.1038/S41592-023-02101-9
ISSN:1548-7091
Dating Alphaproteobacteria evolution with eukaryotic fossils
Sishuo Wang•Haiwei Luo
Nature Communications
2021
•2021/6/3
•Vol.12 No.1 p.1-9
Elucidating the timescale of the evolution of Alphaproteobacteria, one of the most prevalent microbial lineages in marine and terrestrial ecosystems, is key to testing hypotheses on their co-evolution with eukaryotic hosts and Earth’s systems, which, however, is largely limited by the scarcity of ba...
Bacterial evolutionMolecular evolutionParasite evolutionPhylogenetics
10.1038/S41467-021-23645-4
ISSN:2041-1723
Reward system activation improves recovery from acute myocardial infarction
H. Haykin•E. Avishai•M. Krot•M. Ghiringhelli•M. Reshef等 13 人
Nature Cardiovascular Research
2024
•2024/7/12
•Vol.3 No.7 p.841-856
Psychological processes have a crucial role in the recovery from acute myocardial infarction (AMI), yet the underlying mechanisms of these effects remain elusive. Here we demonstrate the impact of the reward system, a brain network associated with motivation and positive expectations, on the clinica...
AngiogenesisMyocardial infarctionNeurosciencePreclinical research
10.1038/S44161-024-00491-3
ISSN:2731-0590
mTORC1 couples cyst(e)ine availability with GPX4 protein synthesis and ferroptosis regulation
Yilei Zhang•Robert V. Swanda•Litong Nie•Xiaoguang Liu•Chao Wang等 17 人
Nature Communications
2021
•2021/3/11
•Vol.12 No.1 p.1-14
Glutathione peroxidase 4 (GPX4) utilizes glutathione (GSH) to detoxify lipid peroxidation and plays an essential role in inhibiting ferroptosis. As a selenoprotein, GPX4 protein synthesis is highly inefficient and energetically costly. How cells coordinate GPX4 synthesis with nutrient availability r...
Cancer therapyCell deathNutrient signallingTranslation
10.1038/S41467-021-21841-W
ISSN:2041-1723
Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing
Ma Xiao-Ru•Zhu Xudong•Xiao Yujie•Gu Hui-Min•Zheng Shuang-Shuang等 25 人
Nature Communications
2022
•2022/3/9
•Vol.13 No.1 p.1-19
The age-dependent decline in remyelination potential of the central nervous system during ageing is associated with a declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). The molecular players that can enhance OPC differentiation or rejuvenate OPCs are unclear. Here we show ...
Multiple sclerosisOligodendrocyteSenescence
10.1038/S41467-022-28844-1
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
Selective inhibitors of JAK1 targeting an isoform-restricted allosteric cysteine
Kavanagh Madeline E.•Horning Benjamin D.•Khattri Roli•Roy Nilotpal•Lu Justine P.等 19 人
Nature Chemical Biology
2022
•2022/9/12
•Vol.18 No.12 p.1388-1398
The Janus tyrosine kinase (JAK) family of non-receptor tyrosine kinases includes four isoforms (JAK1, JAK2, JAK3, and TYK2) and is responsible for signal transduction downstream of diverse cytokine receptors. JAK inhibitors have emerged as important therapies for immun(onc)ological disorders, but th...
Cell signallingImmunologyProteomicsSmall molecules
10.1038/S41589-022-01098-0
ISSN:1552-4450
Declining metal availability in the Mesozoic seawater reflected in phytoplankton succession
Zhang Qiong•Bendif El Mahdi•Zhou Yu•Nevado Bruno•Shafiee Roxana等 6 人
Nature Geoscience
2022
•2022/10/31
•Vol.15 No.11 p.932-941
Variable trace metal concentrations in the Precambrian ocean were closely linked to oxygen availability, although less is known about the drivers of seawater trace metal chemistry after the spread of complex life into the Phanerozoic eon. A major phytoplankton succession took place at the transition...
Element cyclesMarine biology
10.1038/S41561-022-01053-7
ISSN:1752-0894
Histone demethylase KDM5D upregulation drives sex differences in colon cancer
Jiexi Li•Zhengdao Lan•Wenting Liao•James W. Horner•Xueping Xu等 23 人
Nature
2023
•2023/6/21
•00 p.1-8
Sex exerts a profound impact on cancer incidence, spectrum and outcomes, yet the molecular and genetic bases of such sex differences are ill-defined and presumptively ascribed to X-chromosome genes and sex hormones1. Such sex differences are particularly prominent in colorectal cancer (CRC) in which...
Cancer epigeneticsCancer microenvironmentColorectal cancerMetastasis
10.1038/S41586-023-06254-7
ISSN:0028-0836
Microbial iron oxide respiration coupled to sulfide oxidation
Song-Can Chen•Xiao-Min Li•Nicola Battisti•Guoqing Guan•Maria A. Montoya等 13 人
Nature
2025
•2025/8/27
•00 p.1-9
Microorganisms have driven Earth’s sulfur cycle since the emergence of life1–6, yet the sulfur-cycling capacities of microorganisms and their integration with other element cycles remain incompletely understood. One such uncharacterized metabolism is the coupling of sulfide oxidation with iron(iii) ...
Element cyclesEnvironmental microbiology
10.1038/S41586-025-09467-0
ISSN:0028-0836
Deubiquitinating enzymes and the proteasome regulate preferential sets of ubiquitin substrates
Trulsson Fredrik•Akimov Vyacheslav•Robu Mihaela•van Overbeek Nila•Berrocal David Aureliano Pérez等 10 人
Nature Communications
2022
•2022/5/18
•Vol.13 No.1 p.1-17
The ubiquitin-proteasome axis has been extensively explored at a system-wide level, but the impact of deubiquitinating enzymes (DUBs) on the ubiquitinome remains largely unknown. Here, we compare the contributions of the proteasome and DUBs on the global ubiquitinome, using UbiSite technology, inhib...
PolyADP-ribosylationProteomicsSumoylationUbiquitylation
10.1038/S41467-022-30376-7
ISSN:2041-1723
Comparative analysis of two paradigm bacteriophytochromes reveals opposite functionalities in two-component signaling
Elina Multamäki•Rahul Nanekar•Dmitry Morozov•Topias Lievonen•David Golonka等 13 人
Nature Communications
2021
•2021/7/20
•Vol.12 No.1 p.1-14
Bacterial phytochrome photoreceptors usually belong to two-component signaling systems which transmit environmental stimuli to a response regulator through a histidine kinase domain. Phytochromes switch between red light-absorbing and far-red light-absorbing states. Despite exhibiting extensive stru...
Bacterial structural biologyEnzyme mechanismsKinasesX-ray crystallography
10.1038/S41467-021-24676-7
ISSN:2041-1723
Clinical functional proteomics of intercellular signalling in pancreatic cancer
Peiwu Huang•Weina Gao•Changying Fu•Min Wang•Yunguang Li等 18 人
Nature
2024
•2024/11/13
•00 p.1-10
Pancreatic ductal adenocarcinoma (PDAC) has an atypical, highly stromal tumour microenvironment (TME) that profoundly contributes to its poor prognosis1. Here, to better understand the intercellular signalling between cancer and stromal cells directly in PDAC tumours, we developed a multidimensional...
Cancer microenvironmentPancreatic cancerProtein–protein interaction networks
10.1038/S41586-024-08225-Y
ISSN:0028-0836
CLN3 is required for the clearance of glycerophosphodiesters from lysosomes
Laqtom Nouf N.•Dong Wentao•Medoh Uche N.•Cangelosi Andrew L.•Dharamdasani Vimisha等 16 人
Nature
2022
•2022/9/21
•Vol.609 No.7929 p.1005-1011
Lysosomes have many roles, including degrading macromolecules and signalling to the nucleus1. Lysosomal dysfunction occurs in various human conditions, such as common neurodegenerative diseases and monogenic lysosomal storage disorders (LSDs)2–4. For most LSDs, the causal genes have been identified ...
LysosomesMechanisms of disease
10.1038/S41586-022-05221-Y
ISSN:0028-0836
Endothelial discoidin domain receptor 1 senses flow to modulate YAP activation
Jiayu Liu•Chuanrong Zhao•Xue Xiao•Aohan Li•Yueqi Liu等 12 人
Nature Communications
2023
•2023/10/13
•Vol.14 No.1 p.1-20
Mechanotransduction in endothelial cells is critical to maintain vascular homeostasis and can contribute to disease development, yet the molecules responsible for sensing flow remain largely unknown. Here, we demonstrate that the discoidin domain receptor 1 (DDR1) tyrosine kinase is a direct mechano...
Cardiovascular biologyCell biology
10.1038/S41467-023-42341-Z
ISSN:2041-1723
Lipid-mediated activation of plasma membrane-localized deubiquitylating enzymes modulate endosomal trafficking
Vogel Karin•Bläske Tobias•Nagel Marie-Kristin•Globisch Christoph•Maguire Shane等 11 人
Nature Communications
2022
•2022/11/12
•Vol.13 No.1 p.1-19
The abundance of plasma membrane-resident receptors and transporters has to be tightly regulated by ubiquitin-mediated endosomal degradation for the proper coordination of environmental stimuli and intracellular signaling. Arabidopsis OVARIAN TUMOR PROTEASE (OTU) 11 and OTU12 are plasma membrane-loc...
Confocal microscopyPost-translational modificationsProteasesProtein trafficking in plants
10.1038/S41467-022-34637-3
ISSN:2041-1723
Selective bioorthogonal probe for N-glycan hybrid structures
Mana Mohan Mukherjee•Devin Biesbrock•Lara K. Abramowitz•Matteo Pavan•Bhoj Kumar等 9 人
Nature Chemical Biology
2024
•2024/10/28
•00 p.1-12
Metabolic incorporation of chemically tagged monosaccharides is a facile means of tagging cellular glycoproteins and glycolipids. However, since the monosaccharide precursors are often shared by several pathways, selectivity has been difficult to attain. For example, N-linked glycosylation is a chem...
Chemical modificationChemical toolsGlycobiologyMembrane trafficking
10.1038/S41589-024-01756-5
ISSN:1552-4450
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
Deficiency in coatomer complex I causes aberrant activation of STING signalling
Steiner Annemarie•Hrovat-Schaale Katja•Prigione Ignazia•Yu Chien-Hsiung•Laohamonthonkul Pawat等 19 人
Nature Communications
2022
•2022/4/28
•Vol.13 No.1 p.1-16
Coatomer complex I (COPI) mediates retrograde vesicular trafficking from Golgi to the endoplasmic reticulum (ER) and within Golgi compartments. Deficiency in subunit alpha causes COPA syndrome and is associated with type I IFN signalling, although the upstream innate immune sensor involved was unkno...
Autoinflammatory syndromeInflammationPattern recognition receptorsRIG-I-like receptors
10.1038/S41467-022-29946-6
ISSN:2041-1723
Alternatively spliced exon regulates context-dependent MEF2D higher-order assembly during myogenesis
Gönczi Mónika•Teixeira João M. C.•Barrera-Vilarmau Susana•Mediani Laura•Antoniani Francesco等 15 人
Nature Communications
2023
•2023/3/10
•Vol.14 No.1 p.1-13
During muscle cell differentiation, the alternatively spliced, acidic β-domain potentiates transcription of Myocyte-specific Enhancer Factor 2 (Mef2D). Sequence analysis by the FuzDrop method indicates that the β-domain can serve as an interaction element for Mef2D higher-order assembly. In accord, ...
Cell biologyComputational biology and bioinformaticsStructural biology
10.1038/S41467-023-37017-7
ISSN:2041-1723
Proteome-wide and matrisome-specific alterations during human pancreas development and maturation
Zihui Li•Daniel M. Tremmel•Fengfei Ma•Qinying Yu•Min Ma等 14 人
Nature Communications
2021
•2021/2/15
•Vol.12 No.1 p.1-12
The extracellular matrix (ECM) is unique to each tissue and capable of guiding cell differentiation, migration, morphology, and function. The ECM proteome of different developmental stages has not been systematically studied in the human pancreas. In this study, we apply mass spectrometry-based quan...
AgeingExtracellular matrixPancreasProteomics
10.1038/S41467-021-21261-W
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
An RNA splicing system that excises DNA transposons from animal mRNAs
Long-Wen Zhao•Christopher Nardone•Cindy Chang•Joao A. Paulo•Stephen J. Elledge等 6 人
Nature
2025
•2025/12/10
•00 p.1-9
All genomes have mobile genetic segments called transposable elements (TEs)1. Here we describe a system, which we term SOS splicing, that protects Caenorhabditis elegans and human genes against DNA-transposon-mediated disruption by excising these TEs from host mRNAs. SOS splicing, which seems to ope...
Evolutionary geneticsGene expressionGene regulationGenomic instabilityRNA splicing
10.1038/S41586-025-09853-8
ISSN:0028-0836
Predicting functions of uncharacterized gene products from microbial communities
Yancong Zhang•Amrisha Bhosle•Sena Bae•Kelly Eckenrode•Xueying Huang等 16 人
Nature Biotechnology
2025
•2025/10/15
•00 p.1-16
The majority of genes in microbial communities remain uncharacterized. Here we develop a method to infer putative function for microbial proteins at scale by assessing community-wide multiomics data. We predict high-confidence functions for >443,000 protein families (~82.3% previously uncharacter...
Data integrationGene expressionMicrobiomeProtein function predictionsSoftware
10.1038/S41587-025-02813-7
ISSN:1087-0156
A genome-wide atlas of antibiotic susceptibility targets and pathways to tolerance
Leshchiner Dmitry•Rosconi Federico•Sundaresh Bharathi•Rudmann Emily•Ramirez Luisa Maria Nieto等 17 人
Nature Communications
2022
•2022/6/7
•Vol.13 No.1 p.1-17
Detailed knowledge on how bacteria evade antibiotics and eventually develop resistance could open avenues for novel therapeutics and diagnostics. It is thereby key to develop a comprehensive genome-wide understanding of how bacteria process antibiotic stress, and how modulation of the involved proce...
Antimicrobial resistanceBacterial geneticsSystems analysis
10.1038/S41467-022-30967-4
ISSN:2041-1723
eSIG-Net: an interaction language model that decodes the protein code of single mutations
Xingxin Pan•Aditya Shrawat•Sidharth Raghavan•Chuanpeng Dong•Yuntao Yang等 17 人
Nature Methods
2026
•2026/4/29
•00 p.1-6
Most proteins act through interactions with other molecules, yet predicting how single mutations perturb these interactions—defined as ‘protein codes’—remains a central challenge in computational biology. Here we introduce eSIG-Net, the edgetic mutation sequence-based interaction grammar network, a ...
Computational modelsProgramming languageProtein function predictionsProteome informaticsSequence annotation
10.1038/S41592-026-03086-X
ISSN:1548-7091
SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes
Irwin Jungreis•Rachel Sealfon•Manolis Kellis
Nature Communications
2021
•2021/5/11
•Vol.12 No.1 p.1-20
Despite its clinical importance, the SARS-CoV-2 gene set remains unresolved, hindering dissection of COVID-19 biology. We use comparative genomics to provide a high-confidence protein-coding gene set, characterize evolutionary constraint, and prioritize functional mutations. We select 44 Sarbecoviru...
Comparative genomicsMolecular evolutionSARS-CoV-2Sequence annotation
10.1038/S41467-021-22905-7
ISSN:2041-1723
Recent hybrids recapitulate ancient hybrid outcomes
Samridhi Chaturvedi•Lauren K. Lucas•C. Alex Buerkle•James A. Fordyce•Matthew L. Forister等 7 人
Nature Communications
2020
•2020/5/1
•Vol.11 No.1 p.1-15
Genomic outcomes of hybridization depend on selection and recombination in hybrids. Whether these processes have similar effects on hybrid genome composition in contemporary hybrid zones versus ancient hybrid lineages is unknown. Here we show that patterns of introgression in a contemporary hybrid z...
EntomologyEvolutionary geneticsPopulation geneticsSpeciation
10.1038/S41467-020-15641-X
ISSN:2041-1723
Pathogenic UNC13A variants cause a neurodevelopmental syndrome by impairing synaptic function
Reza Asadollahi•Aisha Ahmad•Paranchai Boonsawat•Jasmine Shahanoor Hinzen•Mareike Lohse等 150 人
Nature Genetics
2025
•2025/10/22
•00 p.1-14
The UNC13A gene encodes a presynaptic protein that is crucial for setting the strength and dynamics of information transfer between neurons. Here we describe a neurodevelopmental syndrome caused by germline coding or splice-site variants in UNC13A. The syndrome presents with variable degrees of deve...
Genetic testingNeurodevelopmental disordersNeuroscience
10.1038/S41588-025-02361-5
ISSN:1061-4036
Calibrated geometric deep learning improves kinase–drug binding predictions
Yunan Luo•Yang Liu•Jian Peng
Nature Machine Intelligence
2023
•2023/11/6
•00 p.1-12
Protein kinases regulate various cellular functions and hold significant pharmacological promise in cancer and other diseases. Although kinase inhibitors are one of the largest groups of approved drugs, much of the human kinome remains unexplored but potentially druggable. Computational approaches, ...
Computational modelsData integrationMachine learningProtein function predictionsVirtual drug screening
10.1038/S42256-023-00751-0
ISSN:2522-5839
RNA codon expansion via programmable pseudouridine editing and decoding
Jiangle Liu•Xueqing Yan•Hao Wu•Ziqin Ji•Ye Shan等 14 人
Nature
2025
•2025/6/25
•00 p.1-11
The incorporation of non-canonical amino acids (ncAAs) enables customized chemistry to tailor protein functions1–3. Genetic code expansion offers a general approach for ncAA encoding by reassigning stop codons as the ‘blank’ codon; however, it is not completely orthogonal to translation termination ...
Chemical modificationRNA
10.1038/S41586-025-09165-X
ISSN:0028-0836
An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress
Taichi Igarashi•Marianne Mazevet•Takaaki Yasuhara•Kimiyoshi Yano•Akifumi Mochizuki等 17 人
Nature Communications
2023
•2023/8/17
•Vol.14 No.1 p.1-22
Activation of the KRAS oncogene is a source of replication stress, but how this stress is generated and how it is tolerated by cancer cells remain poorly understood. Here we show that induction of KRASG12V expression in untransformed cells triggers H3K27me3 and HP1-associated chromatin compaction in...
Cancer modelsMechanisms of disease
10.1038/S41467-023-40578-2
ISSN:2041-1723
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
Neutrophil-derived migrasomes are an essential part of the coagulation system
Dong Jiang•Lin Jiao•Qing Li•Renxiang Xie•Haohao Jia等 16 人
Nature Cell Biology
2024
•2024/7/12
•Vol.26 No.7 p.1110-1123
Migrasomes are organelles that are generated by migrating cells. Here we report the key role of neutrophil-derived migrasomes in haemostasis. We found that a large number of neutrophil-derived migrasomes exist in the blood of mice and humans. Compared with neutrophil cell bodies and platelets, these...
CirculationOrganelles
10.1038/S41556-024-01440-9
ISSN:1465-7392
Positron emission tomography imaging of novel AAV capsids maps rapid brain accumulation
Jai Woong Seo•Elizabeth S. Ingham•Lisa Mahakian•Spencer Tumbale•Bo Wu等 22 人
Nature Communications
2020
•2020/4/30
•Vol.11 No.1 p.1-13
Adeno-associated viruses (AAVs) are typically single-stranded deoxyribonucleic acid (ssDNA) encapsulated within 25-nm protein capsids. Recently, tissue-specific AAV capsids (e.g. PHP.eB) have been shown to enhance brain delivery in rodents via the LY6A receptor on brain endothelial cells. Here, we c...
Molecular imagingPositron-emission tomographyViral tracing
10.1038/S41467-020-15818-4
ISSN:2041-1723
CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease
Pierson Sheila K.•Katz Laura•Williams Reece•Mumau Melanie•Gonzalez Michael等 12 人
Nature Communications
2022
•2022/11/24
•Vol.13 No.1 p.1-13
Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood cytokine storm-driven inflammatory disorder. Interleukin-6 (IL-6) is a known disease driver in some patients, but anti-IL-6 therapy with siltuximab is not effective in all patients, and biomarkers indicating success at ...
Acute inflammationChemokinesPredictive markersProteomic analysis
10.1038/S41467-022-34873-7
ISSN:2041-1723
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
The patatin-like protein PlpD forms structurally dynamic homodimers in the Pseudomonas aeruginosa outer membrane
Sarah E. Hanson•Tyrone Dowdy•Mioara Larion•Matthew Thomas Doyle•Harris D. Bernstein
Nature Communications
2024
•2024/5/23
•Vol.15 No.1 p.1-14
Members of the Omp85 superfamily of outer membrane proteins (OMPs) found in Gram-negative bacteria, mitochondria and chloroplasts are characterized by a distinctive 16-stranded β-barrel transmembrane domain and at least one periplasmic POTRA domain. All previously studied Omp85 proteins promote crit...
BacteriologyBiochemistryBiophysics
10.1038/S41467-024-48756-6
ISSN:2041-1723
De novo design of self-assembling peptides with antimicrobial activity guided by deep learning
Huayang Liu•Zilin Song•Yu Zhang•Bihan Wu•Dinghao Chen等 11 人
Nature Materials
2025
•2025/3/14
•00 p.1-12
Bioinspired materials based on self-assembling peptides are promising for tackling various challenges in biomedical engineering. While contemporary data-driven approaches have led to the discovery of self-assembling peptides with various structures and properties, predicting the functionalities of t...
Bioinspired materialsHigh-throughput screeningProtein designSelf-assembly
10.1038/S41563-025-02164-3
ISSN:1476-1122
Crossover patterning through condensation and coarsening of pro-crossover factors
Liangyu Zhang•Weston Stauffer•Chenshu Liu•Hengyi Shao•Noor Abuzahriyeh等 10 人
Nature Cell Biology
2025
•2025/6/19
•00 p.1-14
Meiotic recombination mixes genetic information from parental genomes, creating unique combinations of alleles. During meiotic prophase, each homologue pair must undergo at least one crossover to segregate faithfully. Only a few recombination intermediates become crossovers, and these are widely spa...
Cell divisionChromosomes
10.1038/S41556-025-01688-9
ISSN:1465-7392
The druggable schizophrenia genome: from repurposing opportunities to unexplored drug targets
Lago Santiago G.•Bahn Sabine
Npj Genomic Medicine
2022
•2022/3/25
•Vol.7 No.1 p.1-13
There have been no new drugs for the treatment of schizophrenia in several decades and treatment resistance represents a major unmet clinical need. The drugs that exist are based on serendipitous clinical observations rather than an evidence-based understanding of disease pathophysiology. In the pre...
GenomePharmaceuticsSchizophreniaTarget identification
10.1038/S41525-022-00290-4
ISSN:2056-7944
Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer
Lei-Jie Dai•Ding Ma•Yu-Zheng Xu•Ming Li•Yu-Wei Li等 13 人
Nature Communications
2023
•2023/8/22
•Vol.14 No.1 p.1-13
The molecular heterogeneity and distinct features of HER2-low breast cancers, particularly in the Chinese population, are not well understood, limiting its precise management in the era of antibody‒drug conjugates. To address this issue, we established a cohort of 434 Chinese patients with HER2-low ...
Breast cancerCancer genomicsTargeted therapiesTumour heterogeneity
10.1038/S41467-023-40715-X
ISSN:2041-1723
Estimating dispensable content in the human interactome
Mohamed Ghadie•Yu Xia
Nature Communications
2019
•2019/7/19
•Vol.10 No.1 p.1-9
Protein-protein interaction (PPI) networks (interactome networks) have successfully advanced our knowledge of molecular function, disease and evolution. While much progress has been made in quantifying errors and biases in experimental PPI datasets, it remains unknown what fraction of the error-free...
Biochemical networksCellular signalling networksComputational modelsMolecular modelling
10.1038/S41467-019-11180-2
ISSN:2041-1723
A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism
J. J. David Ho•Nathan C. Balukoff•Phaedra R. Theodoridis•Miling Wang•Jonathan R. Krieger等 7 人
Nature Communications
2020
•2020/5/29
•Vol.11 No.1 p.1-16
Protein expression evolves under greater evolutionary constraint than mRNA levels, and translation efficiency represents a primary determinant of protein levels during stimuli adaptation. This raises the question as to the translatome remodelers that titrate protein output from mRNA populations. Her...
Regulatory networksTranslation
10.1038/S41467-020-16504-1
ISSN:2041-1723
Caspase-2 is a condensate-mediated deubiquitinase in protein quality control
Yingwei Ge•Lijie Zhou•Yesheng Fu•Lijuan He•Yi Chen等 20 人
Nature Cell Biology
2024
•2024/10/31
•00 p.1-15
Protein ubiquitination plays a critical role in protein quality control in response to cellular stress. The excessive accumulation of ubiquitinated conjugates can be detrimental to cells and is recognized as a hallmark of multiple neurodegenerative diseases. However, an in-depth understanding of how...
Protein quality controlUbiquitylation
10.1038/S41556-024-01522-8
ISSN:1465-7392
Deep embedding and alignment of protein sequences
Llinares-López Felipe•Berthet Quentin•Blondel Mathieu•Teboul Olivier•Vert Jean-Philippe
Nature Methods
2022
•2022/12/15
•Vol.20 No.1 p.104-111
Protein sequence alignment is a key component of most bioinformatics pipelines to study the structures and functions of proteins. Aligning highly divergent sequences remains, however, a difficult task that current algorithms often fail to perform accurately, leaving many proteins or open reading fra...
Machine learningSequence annotation
10.1038/S41592-022-01700-2
ISSN:1548-7091
TNF-α-mediated m6A modification of ELMO1 triggers directional migration of mesenchymal stem cell in ankylosing spondylitis
Xie Zhongyu•Yu Wenhui•Zheng Guan•Li Jinteng•Cen Shuizhong等 16 人
Nature Communications
2021
•2021/9/10
•Vol.12 No.1 p.1-14
Ankylosing spondylitis (AS) is a type of rheumatic disease characterized by chronic inflammation and pathological osteogenesis in the entheses. Previously, we demonstrated that enhanced osteogenic differentiation of MSC from AS patients (AS-MSC) resulted in pathological osteogenesis, and that during...
Ankylosing spondylitisBoneMesenchymal stem cells
10.1038/S41467-021-25710-4
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
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
Gene-level metagenomic architectures across diseases yield high-resolution microbiome diagnostic indicators
Braden T. Tierney•Yingxuan Tan•Aleksandar D. Kostic•Chirag J. Patel
Nature Communications
2021
•2021/5/18
•Vol.12 No.1 p.1-12
We propose microbiome disease “architectures”: linking >1 million microbial features (species, pathways, and genes) to 7 host phenotypes from 13 cohorts using a pipeline designed to identify associations that are robust to analytical model choice. Here, we quantify conservation and heterogeneity in ...
Computational biology and bioinformaticsDiagnostic markersMicrobiome
10.1038/S41467-021-23029-8
ISSN:2041-1723
SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care
Clemens Gutmann•Kaloyan Takov•Sean A. Burnap•Bhawana Singh•Hashim Ali等 37 人
Nature Communications
2021
•2021/6/7
•Vol.12 No.1 p.1-17
Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acu...
Mass spectrometryPrognostic markersSARS-CoV-2
10.1038/S41467-021-23494-1
ISSN:2041-1723
Widely conserved AHL transcription factors are essential for NCR gene expression and nodule development in Medicago
Zhang Senlei•Wang Ting•Lima Rui M.•Pettkó-Szandtner Aladár•Kereszt Attila等 7 人
Nature Plants
2023
•2023/1/9
•Vol.9 No.2 p.280-288
Symbiotic nitrogen fixation by Rhizobium bacteria in the cells of legume root nodules alleviates the need for nitrogen fertilizers. Nitrogen fixation requires the endosymbionts to differentiate into bacteroids which can be reversible or terminal. The latter is controlled by the plant, it is more ben...
Plant molecular biologyRhizobial symbiosis
10.1038/S41477-022-01326-4
ISSN:2055-0278
Multi-omics analysis of human mesenchymal stem cells shows cell aging that alters immunomodulatory activity through the downregulation of PD-L1
Yuchen Gao•Ying Chi•Yunfei Chen•Wentian Wang•Huiyuan Li等 21 人
Nature Communications
2023
•2023/7/20
•Vol.14 No.1 p.1-21
Mesenchymal stem cells (MSCs) possess potent immunomodulatory activity and have been extensively investigated for their therapeutic potential in treating inflammatory disorders. However, the mechanisms underlying the immunosuppressive function of MSCs are not fully understood, hindering the developm...
Data miningImmunosuppressionMesenchymal stem cellsSenescenceTranslational immunology
10.1038/S41467-023-39958-5
ISSN:2041-1723
Oxidative photocatalysis on membranes triggers non-canonical pyroptosis
Chaiheon Lee•Mingyu Park•W. C. Bhashini Wijesinghe•Seungjin Na•Chae Gyu Lee等 16 人
Nature Communications
2024
•2024/5/13
•Vol.15 No.1 p.1-16
Intracellular membranes composing organelles of eukaryotes include membrane proteins playing crucial roles in physiological functions. However, a comprehensive understanding of the cellular responses triggered by intracellular membrane-focused oxidative stress remains elusive. Herein, we report an a...
Cell deathChemical modificationChemical tools
10.1038/S41467-024-47634-5
ISSN:2041-1723
DTIAM: a unified framework for predicting drug-target interactions, binding affinities and drug mechanisms
Zhangli Lu•Guoqiang Song•Huimin Zhu•Chuqi Lei•Xinliang Sun等 10 人
Nature Communications
2025
•2025/3/15
•Vol.16 No.1 p.1-17
Accurate and robust prediction of drug-target interactions (DTIs) plays a vital role in drug discovery but remains challenging due to limited labeled data, cold start problems, and insufficient understanding of mechanisms of action (MoA). Distinguishing activation and inhibition mechanisms is partic...
Computational modelsDrug screeningMachine learning
10.1038/S41467-025-57828-0
ISSN:2041-1723
Interplay of BAF and MLL4 promotes cell type-specific enhancer activation
Young-Kwon Park•Ji-Eun Lee•Zhijiang Yan•Kaitlin McKernan•Tommy O’Haren等 8 人
Nature Communications
2021
•2021/3/12
•Vol.12 No.1 p.1-16
Cell type-specific enhancers are activated by coordinated actions of lineage-determining transcription factors (LDTFs) and chromatin regulators. The SWI/SNF chromatin remodeling complex BAF and the histone H3K4 methyltransferase MLL4 (KMT2D) are both implicated in enhancer activation. However, the i...
Cell biologyDevelopmentEpigeneticsGene expressionGene regulation
10.1038/S41467-021-21893-Y
ISSN:2041-1723
A marine sponge-derived lectin reveals hidden pathway for thrombopoietin receptor activation
Watari Hiromi•Kageyama Hiromu•Masubuchi Nami•Nakajima Hiroya•Onodera Kako等 19 人
Nature Communications
2022
•2022/11/25
•Vol.13 No.1 p.1-11
N-glycan-mediated activation of the thrombopoietin receptor (MPL) under pathological conditions has been implicated in myeloproliferative neoplasms induced by mutant calreticulin, which forms an endogenous receptor-agonist complex that traffics to the cell surface and constitutively activates the re...
CytokinesEnzyme mechanismsImmunoblottingX-ray crystallography
10.1038/S41467-022-34921-2
ISSN:2041-1723
A vaccine targeting lung resident-memory CD4+ T cell phenotype protects against Mycobacterium tuberculosis in mice
Kwang Hyun Ko•Seung-Hun Baek•Hyun Shik Bae•Young Mi Kim•Sun Hwa Gu等 12 人
Npj Vaccines
2025
•2025/7/22
•Vol.10 No.1 p.1-12
Lung-resident memory T (TRM) cells respond rapidly and effectively to respiratory pathogen invasion, suppressing pathogen proliferation. Previously, we identified a defined TLR3 agonist called Nexavant (NVT) and developed a vaccine platform that utilizes it to induce lung TRM. In this study, we aime...
ImmunologyMicrobiology
10.1038/S41541-025-01225-7
ISSN:2059-0105
Genetics of nodulation in Aeschynomene evenia uncovers mechanisms of the rhizobium–legume symbiosis
Johan Quilbé•Léo Lamy•Laurent Brottier•Philippe Leleux•Joël Fardoux等 32 人
Nature Communications
2021
•2021/2/5
•Vol.12 No.1 p.1-14
Among legumes (Fabaceae) capable of nitrogen-fixing nodulation, several Aeschynomene spp. use a unique symbiotic process that is independent of Nod factors and infection threads. They are also distinctive in developing root and stem nodules with photosynthetic bradyrhizobia. Despite the significance...
Agricultural geneticsPlant geneticsRhizobial symbiosis
10.1038/S41467-021-21094-7
ISSN:2041-1723
Inhibitors supercharge kinase turnover through native proteolytic circuits
Natalie S. Scholes•Martino Bertoni•Arnau Comajuncosa-Creus•Katharina Kladnik•Xuefei Guo等 30 人
Nature
2025
•2025/11/26
•00 p.1-10
Targeted protein degradation is a pharmacological strategy that relies on small molecules such as proteolysis-targeting chimeras (PROTACs) or molecular glues, which induce proximity between a target protein and an E3 ubiquitin ligase to prompt target ubiquitination and proteasomal degradation1. Spor...
KinasesMechanism of actionProteolysis
10.1038/S41586-025-09763-9
ISSN:0028-0836
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
Negative trade-off between neoantigen repertoire breadth and the specificity of HLA-I molecules shapes antitumor immunity
Máté Manczinger•Balázs Koncz•Gergő Mihály Balogh•Benjamin Tamás Papp•Leó Asztalos等 8 人
Nature Cancer
2021
•2021/7/8
•00 p.1-12
Human leukocyte antigen class I (HLA-I) genes shape our immune response against pathogens and cancer. Certain HLA-I variants can bind a wider range of peptides than others, a feature that could be favorable against a range of viral diseases. However, the implications of this phenomenon on cancer imm...
CancerCancer genomicsCancer immunotherapyTumour immunology
10.1038/S43018-021-00226-4
ISSN:2662-1347
Fungal kinases and transcription factors regulating brain infection in Cryptococcus neoformans
Kyung-Tae Lee•Joohyeon Hong•Dong-Gi Lee•Minjae Lee•Suyeon Cha等 14 人
Nature Communications
2020
•2020/3/23
•Vol.11 No.1 p.1-15
Cryptococcus neoformans causes fatal fungal meningoencephalitis. Here, we study the roles played by fungal kinases and transcription factors (TFs) in blood-brain barrier (BBB) crossing and brain infection in mice. We use a brain infectivity assay to screen signature-tagged mutagenesis (STM)-based li...
Fungal pathogenesisFungal systems biologyPathogens
10.1038/S41467-020-15329-2
ISSN:2041-1723
Integrated chemoenzymatic synthesis of a comprehensive sulfated ganglioside glycan library to decipher functional sulfoglycomics and sialoglycomics
Zhuojia Xu•Yating Liu•Jialin Liu•Wenjing Ma•Zhumin Zhang等 10 人
Nature Chemistry
2024
•2024/6/6
•Vol.16 No.6 p.881-892
Ganglioside glycans are ubiquitous and complex biomolecules that are involved in a wide range of biological functions and disease processes. Variations in sialylation and sulfation render the structural complexity and diversity of ganglioside glycans, and influence protein–carbohydrate interactions....
Carbohydrate chemistryCarbohydratesCombinatorial librariesEnzymes
10.1038/S41557-024-01540-X
ISSN:1755-4330
Regulatory functions of cellular energy sensor SnRK1 for nitrate signalling through NLP7 repression
Wang Honglei•Han Chao•Wang Jia-Gang•Chu Xiaoqian•Shi Wen等 11 人
Nature Plants
2022
•2022/9/1
•Vol.8 No.9 p.1094-1107
The coordinated metabolism of carbon and nitrogen is essential for optimal plant growth and development. Nitrate is an important molecular signal for plant adaptation to a changing environment, but how nitrate regulates plant growth under carbon deficiency conditions remains unclear. Here we show th...
AbioticPlant signalling
10.1038/S41477-022-01236-5
ISSN:2055-0278
Seagrass genomes reveal ancient polyploidy and adaptations to the marine environment
Xiao Ma•Steffen Vanneste•Jiyang Chang•Luca Ambrosino•Kerrie Barry等 38 人
Nature Plants
2024
•2024/1/26
•00 p.1-16
We present chromosome-level genome assemblies from representative species of three independently evolved seagrass lineages: Posidonia oceanica, Cymodocea nodosa, Thalassia testudinum and Zostera marina. We also include a draft genome of Potamogeton acutifolius, belonging to a freshwater sister linea...
Comparative genomicsConservation biologyGenome evolutionPlant evolution
10.1038/S41477-023-01608-5
ISSN:2055-0278
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
Identification of patient-specific CD4+ and CD8+ T cell neoantigens through HLA-unbiased genetic screens
Cattaneo Chiara M.•Battaglia Thomas•Urbanus Jos•Moravec Ziva•Voogd Rhianne等 11 人
Nature Biotechnology
2023
•2023/1/2
•00 p.1-5
Cancer neoantigens that arise from tumor mutations are drivers of tumor-specific T cell responses, but identification of T cell-recognized neoantigens in individual patients is challenging. Previous methods have restricted antigen discovery to selected HLA alleles, thereby limiting the breadth of ne...
Functional genomicsImmunotherapyTumour immunology
10.1038/S41587-022-01547-0
ISSN:1087-0156
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
Scalable homology detection with ERAST
Yinuo Jiang•Bing He•Zihan Wu•Fang Wang•Tianxu Lv等 11 人
Nature Biotechnology
2026
•2026/4/1
•00 p.1-9
Homology search plays a fundamental role in computational biology, enabling the identification of evolutionary relationships and functional similarities among biological sequences. However, current homology search methods, including BLAST, Foldseek and MMseqs2, often struggle to efficiently and accu...
BioinformaticsDatabasesHigh-throughput screeningSoftware
10.1038/S41587-026-03051-1
ISSN:1087-0156
Natural proteome diversity links aneuploidy tolerance to protein turnover
Julia Muenzner•Pauline Trébulle•Federica Agostini•Henrik Zauber•Christoph B. Messner等 23 人
Nature
2024
•2024/5/22
•00 p.1-9
Accessing the natural genetic diversity of species unveils hidden genetic traits, clarifies gene functions and allows the generalizability of laboratory findings to be assessed. One notable discovery made in natural isolates of Saccharomyces cerevisiae is that aneuploidy—an imbalance in chromosome c...
ChromosomesProteomic analysisProteomics
10.1038/S41586-024-07442-9
ISSN:0028-0836
Annelid adult cell type diversity and their pluripotent cellular origins
Patricia Álvarez-Campos•Helena García-Castro•Elena Emili•Alberto Pérez-Posada•Irene del Olmo等 13 人
Nature Communications
2024
•2024/4/12
•Vol.15 No.1 p.1-22
Many annelids can regenerate missing body parts or reproduce asexually, generating all cell types in adult stages. However, the putative adult stem cell populations involved in these processes, and the diversity of cell types generated by them, are still unknown. To address this, we recover 75,218 s...
Adult stem cellsEvolutionary developmental biologyRegeneration
10.1038/S41467-024-47401-6
ISSN:2041-1723
Immune system-wide Mendelian randomization and triangulation analyses support autoimmunity as a modifiable component in dementia-causing diseases
Lindbohm Joni V.•Mars Nina•Sipilä Pyry N.•Singh-Manoux Archana•Runz Heiko等 11 人
Nature Aging
2022
•2022/10/14
•Vol.2 No.10 p.956-972
Immune system and blood–brain barrier dysfunction are implicated in the development of Alzheimer’s and other dementia-causing diseases, but their causal role remains unknown. We performed Mendelian randomization for 1,827 immune system- and blood–brain barrier-related biomarkers and identified 127 p...
AgeingAutoimmune diseasesDementia
10.1038/S43587-022-00293-X
ISSN:2662-8465
Deep Visual Proteomics defines single-cell identity and heterogeneity
Mund Andreas•Coscia Fabian•Kriston András•Hollandi Réka•Kovács Ferenc等 21 人
Nature Biotechnology
2022
•2022/5/19
•00 p.1-10
Despite the availabilty of imaging-based and mass-spectrometry-based methods for spatial proteomics, a key challenge remains connecting images with single-cell-resolution protein abundance measurements. Here, we introduce Deep Visual Proteomics (DVP), which combines artificial-intelligence-driven im...
Mechanisms of diseaseProteomicsSingle-cell imagingTumour heterogeneity
10.1038/S41587-022-01302-5
ISSN:1087-0156
Palaeoproteomics resolves sloth relationships
Samantha Presslee•Graham J. Slater•François Pujos•Analía M. Forasiepi•Roman Fischer等 26 人
Nature Ecology & Evolution
2019
•2019/6/6
•Vol.3 No.7 p.1121-1130
The living tree sloths Choloepus and Bradypus are the only remaining members of Folivora, a major xenarthran radiation that occupied a wide range of habitats in many parts of the western hemisphere during the Cenozoic, including both continents and the West Indies. Ancient DNA evidence has played on...
Molecular evolutionPalaeontologyPhylogeneticsZoology
10.1038/S41559-019-0909-Z
ISSN:2397-334X
Truncated FGFR2 is a clinically actionable oncogene in multiple cancers
Zingg Daniel•Bhin Jinhyuk•Yemelyanenko Julia•Kas Sjors M.•Rolfs Frank等 48 人
Nature
2022
•2022/8/10
•Vol.608 No.7923 p.609-617
Somatic hotspot mutations and structural amplifications and fusions that affect fibroblast growth factor receptor 2 (encoded by FGFR2) occur in multiple types of cancer1. However, clinical responses to FGFR inhibitors have remained variable1–9, emphasizing the need to better understand which FGFR2 a...
Breast cancerCancer modelsGrowth factor signallingOncogenes
10.1038/S41586-022-05066-5
ISSN:0028-0836
Multiplex and multimodal mapping of variant effects in secreted proteins via MultiSTEP
Nicholas A. Popp•Rachel L. Powell•Melinda K. Wheelock•Kristen J. Holmes•Brendan D. Zapp等 15 人
Nature Structural & Molecular Biology
2025
•2025/6/13
•00 p.1-13
Despite widespread advances in DNA sequencing, the functional consequences of most genetic variants remain poorly understood. Multiplexed assays of variant effect can measure the function of variants at scale but cannot readily be applied to the ~10% of human genes encoding secreted proteins. Here w...
DiseasesGenomicsHigh-throughput screeningProteinsSecretion
10.1038/S41594-025-01582-W
ISSN:1545-9993
A truncating variant of RAD51B associated with primary ovarian insufficiency provides insights into its meiotic and somatic functions
Franca Monica M.•Condezo Yazmine B.•Elzaiat Maëva•Felipe-Medina Natalia•Sánchez-Sáez Fernando等 16 人
Cell Death & Differentiation
2022
•2022/5/27
•00 p.1-15
Primary ovarian insufficiency (POI) causes female infertility by abolishing normal ovarian function. Although its genetic etiology has been extensively investigated, most POI cases remain unexplained. Using whole-exome sequencing, we identified a homozygous variant in RAD51B –(c.92delT) in two siste...
Cell biologyReproductive disorders
10.1038/S41418-022-01021-Z
ISSN:1350-9047
Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation
Anna Rodina•Chao Xu•Chander S. Digwal•Suhasini Joshi•Yogita Patel等 31 人
Nature Communications
2023
•2023/6/23
•Vol.14 No.1 p.1-26
Systems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take ad...
BioinformaticsCancer genomicsChaperonesNetworks and systems biologySystems analysis
10.1038/S41467-023-39241-7
ISSN:2041-1723
Co-evolution-based prediction of metal-binding sites in proteomes by machine learning
Cheng Yao•Wang Haobo•Xu Hua•Liu Yuan•Ma Bin等 13 人
Nature Chemical Biology
2023
•2023/1/2
•00 p.1-8
Metal ions have various important biological roles in proteins, including structural maintenance, molecular recognition and catalysis. Previous methods of predicting metal-binding sites in proteomes were based on either sequence or structural motifs. Here we developed a co-evolution-based pipeline n...
Machine learningMetalloproteinsMetalsProteomics
10.1038/S41589-022-01223-Z
ISSN:1552-4450
Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection
Munnur Deeksha•Teo Qiwen•Eggermont Denzel•Lee Horace H. Y.•Thery Fabien等 17 人
Nature Immunology
2021
•2021/10/18
•00 p.1-12
Ubiquitin-like protein ISG15 (interferon-stimulated gene 15) (ISG15) is a ubiquitin-like modifier induced during infections and involved in host defense mechanisms. Not surprisingly, many viruses encode deISGylating activities to antagonize its effect. Here we show that infection by Zika, SARS-CoV-2...
InfectionSARS-CoV-2
10.1038/S41590-021-01035-8
ISSN:1529-2908
A synthetic cell-free 36-enzyme reaction system for vitamin B12 production
Qian Kang•Huan Fang•Mengjie Xiang•Kaixing Xiao•Pingtao Jiang等 8 人
Nature Communications
2023
•2023/8/24
•Vol.14 No.1 p.1-15
Adenosylcobalamin (AdoCbl), a biologically active form of vitamin B12 (coenzyme B12), is one of the most complex metal-containing natural compounds and an essential vitamin for animals. However, AdoCbl can only be de novo synthesized by prokaryotes, and its industrial manufacturing to date was limit...
BiocatalysisEnzymes
10.1038/S41467-023-40932-4
ISSN:2041-1723
Phylogenetically and functionally diverse microorganisms reside under the Ross Ice Shelf
Martínez-Pérez Clara•Greening Chris•Bay Sean K.•Lappan Rachael J.•Zhao Zihao等 16 人
Nature Communications
2022
•2022/1/10
•Vol.13 No.1 p.1-15
Throughout coastal Antarctica, ice shelves separate oceanic waters from sunlight by hundreds of meters of ice. Historical studies have detected activity of nitrifying microorganisms in oceanic cavities below permanent ice shelves. However, little is known about the microbial composition and pathways...
Classification and taxonomyMarine biologyWater microbiology
10.1038/S41467-021-27769-5
ISSN:2041-1723
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
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
The relaxin receptor RXFP1 signals through a mechanism of autoinhibition
Erlandson Sarah C.•Rawson Shaun•Osei-Owusu James•Brock Kelly P.•Liu Xinyue等 11 人
Nature Chemical Biology
2023
•2023/4/20
•00 p.1-9
The relaxin family peptide receptor 1 (RXFP1) is the receptor for relaxin-2, an important regulator of reproductive and cardiovascular physiology. RXFP1 is a multi-domain G protein-coupled receptor (GPCR) with an ectodomain consisting of a low-density lipoprotein receptor class A (LDLa) module and l...
Cell signallingComputational chemistryG protein-coupled receptorsStructural biology
10.1038/S41589-023-01321-6
ISSN:1552-4450
Hierarchized phosphotarget binding by the seven human 14-3-3 isoforms
Gergo Gogl•Kristina V. Tugaeva•Pascal Eberling•Camille Kostmann•Gilles Trave等 6 人
Nature Communications
2021
•2021/3/15
•Vol.12 No.1 p.1-12
The seven 14-3-3 isoforms are highly abundant human proteins encoded by similar yet distinct genes. 14-3-3 proteins recognize phosphorylated motifs within numerous human and viral proteins. Here, we analyze by X-ray crystallography, fluorescence polarization, mutagenesis and fusicoccin-mediated modu...
Intracellular signalling peptides and proteinsPeptidesPhosphorylationViral proteinsX-ray crystallography
10.1038/S41467-021-21908-8
ISSN:2041-1723
An integrated magneto-electrochemical device for the rapid profiling of tumour extracellular vesicles from blood plasma
Jongmin Park•Jun Seok Park•Chen-Han Huang•Ala Jo•Kaitlyn Cook等 18 人
Nature Biomedical Engineering
2021
•2021/6/28
•00 p.1-12
Assays for cancer diagnosis via the analysis of biomarkers on circulating extracellular vesicles (EVs) typically have lengthy sample workups, limited throughput or insufficient sensitivity, or do not use clinically validated biomarkers. Here we report the development and performance of a 96-well ass...
BiosensorsDiagnostic markers
10.1038/S41551-021-00752-7
ISSN:2157-846X
Accurately predicting optimal conditions for microorganism proteins through geometric graph learning and language model
Mingming Zhu•Yidong Song•Qianmu Yuan•Yuedong Yang
Communications Biology
2024
•2024/12/29
•Vol.7 No.1 p.1-10
Proteins derived from microorganisms that survive in the harshest environments on Earth have stable activity under extreme conditions, providing rich resources for industrial applications and enzyme engineering. Due to the time-consuming nature of experimental determinations, it is imperative to dev...
Computational modelsSequence annotation
10.1038/S42003-024-07436-3
ISSN:2399-3642
Phytate metabolism is mediated by microbial cross-feeding in the gut microbiota
Willem M. De Vos•Minh Nguyen Trung•Mark Davids•Guizhen Liu•Melany Rios-Morales等 9 人
Nature Microbiology
2024
•2024/6/10
•00 p.1-16
Dietary intake of phytate has various reported health benefits. Previous work showed that the gut microbiota can convert phytate to short-chain fatty acids (SCFAs), but the microbial species and metabolic pathway are unclear. Here we identified Mitsuokella jalaludinii as an efficient phytate degrade...
Bacterial genomicsCellular microbiologyPreclinical research
10.1038/S41564-024-01698-7
ISSN:2058-5276
Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling
Xudong Chen•Min Xie•Sensen Zhang•Marta Monguió-Tortajada•Jian Yin等 24 人
Nature Communications
2023
•2023/10/20
•Vol.14 No.1 p.1-13
Toll-like receptors (TLRs) are a class of proteins that play critical roles in recognizing pathogens and initiating innate immune responses. TASL, a recently identified innate immune adaptor protein for endolysosomal TLR7/8/9 signaling, is recruited by the lysosomal proton-coupled amino-acid transpo...
Cryoelectron microscopySignal transduction
10.1038/S41467-023-42210-9
ISSN:2041-1723
Non-canonical function of DGCR8 in DNA double-strand break repair signaling and tumor radioresistance
Qinglei Hang•Liyong Zeng•Li Wang•Litong Nie•Fan Yao等 12 人
Nature Communications
2021
•2021/6/29
•Vol.12 No.1 p.1-18
In response to DNA double-strand breaks (DSBs), repair proteins are recruited to the damaged sites. Ubiquitin signaling plays a critical role in coordinating protein recruitment during the DNA damage response. Here, we find that the microRNA biogenesis factor DGCR8 promotes tumor resistance to X-ray...
Double-strand DNA breaksRadiotherapyUbiquitylation
10.1038/S41467-021-24298-Z
ISSN:2041-1723
Cellular pyrimidine imbalance triggers mitochondrial DNA–dependent innate immunity
Hans-Georg Sprenger•Thomas MacVicar•Amir Bahat•Kai Uwe Fiedler•Steffen Hermans等 13 人
Nature Metabolism
2021
•2021/4/26
•Vol.3 No.5 p.636-650
Cytosolic mitochondrial DNA (mtDNA) elicits a type I interferon response, but signals triggering the release of mtDNA from mitochondria remain enigmatic. Here, we show that mtDNA-dependent immune signalling via the cyclic GMP–AMP synthase‒stimulator of interferon genes‒TANK-binding kinase 1 (cGAS–ST...
DNA metabolismInnate immunityMitochondria
10.1038/S42255-021-00385-9
ISSN:2522-5812
The monoaminergic system is a bilaterian innovation
Matthew Goulty•Gaelle Botton-Amiot•Ezio Rosato•Simon G. Sprecher•Roberto Feuda
Nature Communications
2023
•2023/6/6
•Vol.14 No.1 p.1-15
Monoamines like serotonin, dopamine, and adrenaline/noradrenaline (epinephrine/norepinephrine) act as neuromodulators in the nervous system. They play a role in complex behaviours, cognitive functions such as learning and memory formation, as well as fundamental homeostatic processes such as sleep a...
Evolutionary geneticsHormonesPhylogeneticsSynaptic transmission
10.1038/S41467-023-39030-2
ISSN:2041-1723
Structure and sucrose binding mechanism of the plant SUC1 sucrose transporter
Laust Bavnhøj•Jan Heiner Driller•Lorena Zuzic•Amanda Dyrholm Stange•Birgit Schiøtt等 6 人
Nature Plants
2023
•2023/5/15
•00 p.1-13
Sucrose import from photosynthetic tissues into the phloem is mediated by transporters from the low-affinity sucrose transporter family (SUC/SUT family). Furthermore, sucrose redistribution to other tissues is driven by phloem sap movement, the product of high turgor pressure created by this import ...
Plant molecular biologyPlant sciences
10.1038/S41477-023-01421-0
ISSN:2055-0278
Mass spectrometry-based draft of the mouse proteome
Giansanti Piero•Samaras Patroklos•Bian Yangyang•Meng Chen•Coluccio Andrea等 31 人
Nature Methods
2022
•2022/6/16
•00 p.1-9
The laboratory mouse ranks among the most important experimental systems for biomedical research and molecular reference maps of such models are essential informational tools. Here, we present a quantitative draft of the mouse proteome and phosphoproteome constructed from 41 healthy tissues and seve...
ProteomicsSystems biology
10.1038/S41592-022-01526-Y
ISSN:1548-7091
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
Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans
Ravindra Kodihalli C.•Vaidya Vishal S.•Wang Zhenyu•Federspiel Joel D.•Virgen-Slane Richard等 28 人
Nature Communications
2023
•2023/3/3
•Vol.14 No.1 p.1-14
Diagnosis of drug-induced liver injury (DILI) and its distinction from other liver diseases are significant challenges in drug development and clinical practice. Here, we identify, confirm, and replicate the biomarker performance characteristics of candidate proteins in patients with DILI at onset (...
Diagnostic markersLiver diseasesPrognostic markersProteomics
10.1038/S41467-023-36858-6
ISSN:2041-1723
Data-independent acquisition boosts quantitative metaproteomics for deep characterization of gut microbiota
Zhao Jinzhi•Yang Yi•Xu Hua•Zheng Jianxujie•Shen Chengpin等 14 人
Npj Biofilms And Microbiomes
2023
•2023/1/24
•Vol.9 No.1 p.1-14
Metaproteomics can provide valuable insights into the functions of human gut microbiota (GM), but is challenging due to the extreme complexity and heterogeneity of GM. Data-independent acquisition (DIA) mass spectrometry (MS) has been an emerging quantitative technique in conventional proteomics, bu...
Biological techniquesMicrobiome
10.1038/S41522-023-00373-9
ISSN:2055-5008
Design of diverse, functional mitochondrial targeting sequences across eukaryotic organisms using variational autoencoder
Aashutosh Girish Boob•Shih-I Tan•Airah Zaidi•Nilmani Singh•Xueyi Xue等 9 人
Nature Communications
2025
•2025/5/4
•Vol.16 No.1 p.1-16
Mitochondria play a key role in energy production and metabolism, making them a promising target for metabolic engineering and disease treatment. However, despite the known influence of passenger proteins on localization efficiency, only a few protein-localization tags have been characterized for mi...
Computational modelsMachine learningMetabolic engineeringSynthetic biology
10.1038/S41467-025-59499-3
ISSN:2041-1723
Large-scale computational discovery and analysis of virus-derived microbial nanocompartments
Andreas Michael P.•Giessen Tobias W.
Nature Communications
2021
•2021/8/6
•Vol.12 No.1 p.1-16
Encapsulins are a class of microbial protein compartments defined by the viral HK97-fold of their capsid protein, self-assembly into icosahedral shells, and dedicated cargo loading mechanism for sequestering specific enzymes. Encapsulins are often misannotated and traditional sequence-based searches...
ArchaeaBacteriaBiochemistryCellular microbiology
10.1038/S41467-021-25071-Y
ISSN:2041-1723
Phosphatidylinositides regulate the cell plate morphology transition during cytokinesis in Arabidopsis
Yu Luo•Yu-Fang Tian•Hui-Ru Liu•Wei-Cai Yang
Nature Communications
2025
•2025/7/30
•Vol.16 No.1 p.1-16
In plants, the developing cell plate which is characterized by a series of anionic lipids, undergoes dramatic morphological change for successful cytokinesis. However, the mechanisms underlying these alterations, and the roles of anionic lipids such as phosphatidylinositol-4-phosphate (PI4P), phosph...
CytokinesisPlant cell biologyPlant molecular biology
10.1038/S41467-025-62067-4
ISSN:2041-1723
Protein-Peptide Turnover Profiling reveals the order of PTM addition and removal during protein maturation
Hammarén Henrik M.•Geissen Eva-Maria•Potel Clement M.•Beck Martin•Savitski Mikhail M.
Nature Communications
2022
•2022/12/2
•Vol.13 No.1 p.1-15
Post-translational modifications (PTMs) regulate various aspects of protein function, including degradation. Mass spectrometric methods relying on pulsed metabolic labeling are popular to quantify turnover rates on a proteome-wide scale. Such data have traditionally been interpreted in the context o...
Mass spectrometryPhosphorylationProtein analysisProteomic analysisProteomics
10.1038/S41467-022-35054-2
ISSN:2041-1723
Genome sequencing reveals the genetic architecture of heterostyly and domestication history of common buckwheat
Jeffrey A. Fawcett•Ryoma Takeshima•Shinji Kikuchi•Euki Yazaki•Tomoyuki Katsube-Tanaka等 28 人
Nature Plants
2023
•2023/8/10
•Vol.9 No.8 p.1236-1251
Common buckwheat, Fagopyrum esculentum, is an orphan crop domesticated in southwest China that exhibits heterostylous self-incompatibility. Here we present chromosome-scale assemblies of a self-compatible F. esculentum accession and a self-compatible wild relative, Fagopyrum homotropicum, together w...
Genome duplicationPlant domesticationPlant genetics
10.1038/S41477-023-01474-1
ISSN:2055-0278
Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer
Nuno Apóstolo•Samuel N. Smukowski•Jeroen Vanderlinden•Giuseppe Condomitti•Vasily Rybakin等 14 人
Nature Communications
2020
•2020/10/14
•Vol.11 No.1 p.1-21
Excitatory and inhibitory neurons are connected into microcircuits that generate circuit output. Central in the hippocampal CA3 microcircuit is the mossy fiber (MF) synapse, which provides powerful direct excitatory input and indirect feedforward inhibition to CA3 pyramidal neurons. Here, we dissect...
Cellular neuroscienceDevelopment of the nervous systemMolecular neuroscienceNeural circuitsSynaptic development
10.1038/S41467-020-18956-X
ISSN:2041-1723
Tumour-reactive heterotypic CD8 T cell clusters from clinical samples
Sofía Ibáñez-Molero•Johanna Veldman•Juan Simon Nieto•Joleen J. H. Traets•Austin George等 28 人
Nature
2025
•2025/11/19
•00 p.1-10
Emerging evidence suggests a correlation between CD8+ T cell–tumour cell proximity and anti-tumour immune response1,2. However, it remains unclear whether these cells exist as functional clusters that can be isolated from clinical samples. Here, using conventional and imaging flow cytometry, we show...
Cancer microenvironmentTumour immunology
10.1038/S41586-025-09754-W
ISSN:0028-0836
Integrated omics in Drosophila uncover a circadian kinome
Chenwei Wang•Ke Shui•Shanshan Ma•Shaofeng Lin•Ying Zhang等 12 人
Nature Communications
2020
•2020/6/1
•Vol.11 No.1 p.1-15
Most organisms on the earth exhibit circadian rhythms in behavior and physiology, which are driven by endogenous clocks. Phosphorylation plays a central role in timing the clock, but how this contributes to overt rhythms is unclear. Here we conduct phosphoproteomics in conjunction with transcriptomi...
Computational biology and bioinformaticsGeneticsSystems biology
10.1038/S41467-020-16514-Z
ISSN:2041-1723
Systematic evaluation of AML-associated antigens identifies anti-U5 SNRNP200 therapeutic antibodies for the treatment of acute myeloid leukemia
Katherine Knorr•Jahan Rahman•Caroline Erickson•Eric Wang•Mara Monetti等 26 人
Nature Cancer
2023
•2023/10/23
•00 p.1-18
Despite recent advances in the treatment of acute myeloid leukemia (AML), there has been limited success in targeting surface antigens in AML, in part due to shared expression across malignant and normal cells. Here, high-density immunophenotyping of AML coupled with proteogenomics identified unique...
Acute myeloid leukaemiaApplied immunologyCancerCancer therapyImmunotherapy
10.1038/S43018-023-00656-2
ISSN:2662-1347
Engineering substrate specificity of HAD phosphatases and multienzyme systems development for the thermodynamic-driven manufacturing sugars
Tian Chaoyu•Yang Jiangang•Liu Cui•Chen Peng•Zhang Tong等 9 人
Nature Communications
2022
•2022/6/23
•Vol.13 No.1 p.1-13
Naturally, haloacid dehalogenase superfamily phosphatases have been evolved with broad substrate promiscuity; however, strong specificity to a particular substrate is required for developing thermodynamically driven routes for manufacturing sugars. How to alter the intrinsic substrate promiscuity of...
BiocatalysisGlycobiologyHydrolasesMonosaccharidesMultienzyme complexes
10.1038/S41467-022-31371-8
ISSN:2041-1723
E2–Ub-R74G strategy reveals E2-specific ubiquitin conjugation profiles in live cells
Siqi Shen•Hang Yin
Nature Chemical Biology
2025
•2025/1/6
•00 p.1-11
The E2 ubiquitin (Ub)-conjugating enzyme primarily determines Ub conjugation as Ub-isopeptide (lysine), Ub-oxyester (serine/threonine) or Ub-thioester (cysteine). However, E2-specific Ub conjugation profiles within cells remain elusive. Here we developed the fusion E2–Ub-R74G profiling (FUSEP) strat...
Chemical biologyChemical tools
10.1038/S41589-024-01809-9
ISSN:1552-4450
A generative artificial intelligence approach for the discovery of antimicrobial peptides against multidrug-resistant bacteria
Yihui Wang•Lanlan Zhao•Ziyun Li•Yaxuan Xi•Yingmiao Pan等 7 人
Nature Microbiology
2025
•2025/10/3
•00 p.1-16
The discovery of novel antimicrobial peptides (AMPs) against clinical superbugs is urgently needed to address the ongoing antibiotic resistance crisis. AMPs are promising candidates due to their broad-spectrum activity, rapid bactericidal mechanisms and reduced likelihood of inducing resistance comp...
AntibioticsAntimicrobial resistanceData miningHigh-throughput screening
10.1038/S41564-025-02114-4
ISSN:2058-5276
Synergistic biodegradation of aromatic-aliphatic copolyester plastic by a marine microbial consortium
Ingrid E. Meyer-Cifuentes•Johannes Werner•Nico Jehmlich•Sabine E. Will•Meina Neumann-Schaal等 6 人
Nature Communications
2020
•2020/11/13
•Vol.11 No.1 p.1-13
The degradation of synthetic polymers by marine microorganisms is not as well understood as the degradation of plastics in soil and compost. Here, we use metagenomics, metatranscriptomics and metaproteomics to study the biodegradation of an aromatic-aliphatic copolyester blend by a marine microbial ...
Applied microbiologyMetagenomics
10.1038/S41467-020-19583-2
ISSN:2041-1723
Divergent genomic trajectories predate the origin of animals and fungi
Ocaña-Pallarès Eduard•Williams Tom A.•López-Escardó David•Arroyo Alicia S.•Pathmanathan Jananan S.等 10 人
Nature
2022
•2022/8/24
•Vol.609 No.7928 p.747-753
Animals and fungi have radically distinct morphologies, yet both evolved within the same eukaryotic supergroup: Opisthokonta1,2. Here we reconstructed the trajectory of genetic changes that accompanied the origin of Metazoa and Fungi since the divergence of Opisthokonta with a dataset that includes ...
Computational biology and bioinformaticsMicrobiologyMolecular evolution
10.1038/S41586-022-05110-4
ISSN:0028-0836
A perfusable, multifunctional epicardial device improves cardiac function and tissue repair
Shixing Huang•Dong Lei•Qi Yang•Yang Yang•Chenyu Jiang等 17 人
Nature Medicine
2021
•2021/3/15
•Vol.27 No.3 p.480-490
Despite advances in technologies for cardiac repair after myocardial infarction (MI), new integrated therapeutic approaches still need to be developed. In this study, we designed a perfusable, multifunctional epicardial device (PerMed) consisting of a biodegradable elastic patch (BEP), permeable hie...
Biomedical engineeringDrug deliveryMyocardial infarction
10.1038/S41591-021-01279-9
ISSN:1078-8956
Integrated multi-omics for rapid rare disease diagnosis on a national scale
Sebastian Lunke•Sophie E. Bouffler•Chirag V. Patel•Sarah A. Sandaradura•Meredith Wilson等 44 人
Nature Medicine
2023
•2023/6/8
•00 p.1-11
Critically ill infants and children with rare diseases need equitable access to rapid and accurate diagnosis to direct clinical management. Over 2 years, the Acute Care Genomics program provided whole-genome sequencing to 290 families whose critically ill infants and children were admitted to hospit...
DiseasesGenetics researchTranslational research
10.1038/S41591-023-02401-9
ISSN:1078-8956
Citrullination modulates antigen processing and presentation by revealing cryptic epitopes in rheumatoid arthritis
Curran Ashley M.•Girgis Alexander A.•Jang Yura•Crawford Jonathan D.•Thomas Mekha A.等 10 人
Nature Communications
2023
•2023/2/24
•Vol.14 No.1 p.1-17
Cryptic peptides, hidden from the immune system under physiologic conditions, are revealed by changes to MHC class II processing and hypothesized to drive the loss of immune tolerance to self-antigens in autoimmunity. Rheumatoid arthritis (RA) is an autoimmune disease characterized by immune respons...
Antigen processing and presentationAutoimmunityPost-translational modificationsRheumatoid arthritisTranslational immunology
10.1038/S41467-023-36620-Y
ISSN:2041-1723
Fonio millet genome unlocks African orphan crop diversity for agriculture in a changing climate
Michael Abrouk•Hanin Ibrahim Ahmed•Philippe Cubry•Denisa Šimoníková•Stéphane Cauet等 28 人
Nature Communications
2020
•2020/9/8
•Vol.11 No.1 p.1-13
Sustainable food production in the context of climate change necessitates diversification of agriculture and a more efficient utilization of plant genetic resources. Fonio millet (Digitaria exilis) is an orphan African cereal crop with a great potential for dryland agriculture. Here, we establish hi...
Agricultural geneticsGenetic variationPlant breedingPlant domestication
10.1038/S41467-020-18329-4
ISSN:2041-1723
Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma
Kropivsek Klara•Kachel Paul•Goetze Sandra•Wegmann Rebekka•Festl Yasmin等 14 人
Nature Cancer
2023
•2023/4/20
•00 p.1-20
Multiple myeloma (MM) is a plasma cell malignancy defined by complex genetics and extensive patient heterogeneity. Despite a growing arsenal of approved therapies, MM remains incurable and in need of guidelines to identify effective personalized treatments. Here, we survey the ex vivo drug and immun...
CancerCancer therapyMyelomaPhenotypic screening
10.1038/S43018-023-00544-9
ISSN:2662-1347
UniKP: a unified framework for the prediction of enzyme kinetic parameters
Han Yu•Huaxiang Deng•Jiahui He•Jay D. Keasling•Xiaozhou Luo
Nature Communications
2023
•2023/12/11
•Vol.14 No.1 p.1-13
Prediction of enzyme kinetic parameters is essential for designing and optimizing enzymes for various biotechnological and industrial applications, but the limited performance of current prediction tools on diverse tasks hinders their practical applications. Here, we introduce UniKP, a unified frame...
Computational modelsEnzymesMetabolomicsProtein designSynthetic biology
10.1038/S41467-023-44113-1
ISSN:2041-1723
Conversion of dietary inositol into propionate and acetate by commensal Anaerostipes associates with host health
Bui Thi Phuong Nam•Mannerås-Holm Louise•Puschmann Robert•Wu Hao•Troise Antonio Dario等 10 人
Nature Communications
2021
•2021/8/10
•Vol.12 No.1 p.1-16
We describe the anaerobic conversion of inositol stereoisomers to propionate and acetate by the abundant intestinal genus Anaerostipes. A inositol pathway was elucidated by nuclear magnetic resonance using [13C]-inositols, mass spectrometry and proteogenomic analyses in A. rhamnosivorans, identifyin...
Bacterial genomicsBacterial physiology
10.1038/S41467-021-25081-W
ISSN:2041-1723
A LHCB9-dependent photosystem I megacomplex induced under low light in Physcomitrella patens
Alberta Pinnola•Alessandro Alboresi•Lukáš Nosek•Dmitry Semchonok•Arshad Rameez等 12 人
Nature Plants
2018
•2018/10/29
•Vol.4 No.11 p.910-919
Photosystem I of the moss Physcomitrella patens has special properties, including the capacity to undergo non-photochemical fluorescence quenching. We studied the organization of photosystem I under different light and carbon supply conditions in wild-type moss and in moss with the lhcb9 (light-harv...
EcophysiologyLight responsesPhotosynthesisPlant evolution
10.1038/S41477-018-0270-2
ISSN:2055-0278
Analysis of the Coptis chinensis genome reveals the diversification of protoberberine-type alkaloids
Yifei Liu•Bo Wang•Shaohua Shu•Zheng Li•Chi Song等 26 人
Nature Communications
2021
•2021/6/2
•Vol.12 No.1 p.1-13
Chinese goldthread (Coptis chinensis Franch.), a member of the Ranunculales, represents an important early-diverging eudicot lineage with diverse medicinal applications. Here, we present a high-quality chromosome-scale genome assembly and annotation of C. chinensis. Phylogenetic and comparative geno...
Genome evolutionNext-generation sequencingPlant evolutionSecondary metabolism
10.1038/S41467-021-23611-0
ISSN:2041-1723
Genoppi is an open-source software for robust and standardized integration of proteomic and genetic data
Greta Pintacuda•Frederik H. Lassen•Yu-Han H. Hsu•April Kim•Jacqueline M. Martín等 10 人
Nature Communications
2021
•2021/5/10
•Vol.12 No.1 p.1-10
Combining genetic and cell-type-specific proteomic datasets can generate biological insights and therapeutic hypotheses, but a technical and statistical framework for such analyses is lacking. Here, we present an open-source computational tool called Genoppi (lagelab.org/genoppi) that enables robust...
Amyotrophic lateral sclerosisProtein–protein interaction networksProteome informatics
10.1038/S41467-021-22648-5
ISSN:2041-1723
CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis
Zihan Tang•Yanyan Xu•Yun Tan•Hui Shi•Peipei Jin等 25 人
Nature Communications
2023
•2023/8/21
•Vol.14 No.1 p.1-13
Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administr...
Mechanisms of diseaseResearch dataViral infection
10.1038/S41467-023-40824-7
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
Functional synapses between neurons and small cell lung cancer
Vignesh Sakthivelu•Anna Schmitt•Franka Odenthal•Kristiano Ndoci•Marian Touet等 75 人
Nature
2025
•2025/9/10
•00 p.1-11
Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer, characterized by rapid proliferation, early metastatic spread, frequent early relapse and a high mortality rate1–3. Recent evidence has suggested that innervation has an important role in the development and progression o...
Cancer genomicsCancer microenvironmentNeuroscienceSmall-cell lung cancerTargeted therapies
10.1038/S41586-025-09434-9
ISSN:0028-0836
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
A data-independent acquisition-based global phosphoproteomics system enables deep profiling
Reta Birhanu Kitata•Wai-Kok Choong•Chia-Feng Tsai•Pei-Yi Lin•Bo-Shiun Chen等 9 人
Nature Communications
2021
•2021/5/5
•Vol.12 No.1 p.1-14
Phosphoproteomics can provide insights into cellular signaling dynamics. To achieve deep and robust quantitative phosphoproteomics profiling for minute amounts of sample, we here develop a global phosphoproteomics strategy based on data-independent acquisition (DIA) mass spectrometry and hybrid spec...
Mass spectrometryNon-small-cell lung cancerPhosphorylationProteomics
10.1038/S41467-021-22759-Z
ISSN:2041-1723
circIPO7 dissociates caprin-1 from ribosomes and inhibits gastric cancer cell proliferation by suppressing EGFR and mTOR
Liu Jing•Niu Liling•Hao Jiaru•Yao Yuan•Yan Meinan等 6 人
Oncogene
2023
•2023/2/3
•00 p.1-14
Circular RNA (circRNA) is a novel RNA molecule characterized by covalently closed loop structure. Since its discovery, researchers have shown that circRNA is not “splicing noise” but a participant of various pathophysiological processes through unique mechanisms. circIPO7, which was identified as an...
Cell growthGastric cancerNon-coding RNAsTranslation
10.1038/S41388-023-02610-Z
ISSN:0950-9232
SQANTI3: curation of long-read transcriptomes for accurate identification of known and novel isoforms
Francisco J. Pardo-Palacios•Angeles Arzalluz-Luque•Liudmyla Kondratova•Pedro Salguero•Jorge Mestre-Tomás等 12 人
Nature Methods
2024
•2024/3/20
•00 p.1-5
SQANTI3 is a tool designed for the quality control, curation and annotation of long-read transcript models obtained with third-generation sequencing technologies. Leveraging its annotation framework, SQANTI3 calculates quality descriptors of transcript models, junctions and transcript ends. With thi...
Data miningSoftware
10.1038/S41592-024-02229-2
ISSN:1548-7091
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
Phagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria
Musasia Fauzia K.•Nkumama Irene N.•Frank Roland•Kipkemboi Victor•Schneider Martin等 16 人
Nature Communications
2022
•2022/7/14
•Vol.13 No.1 p.1-12
Ring-infected erythrocytes are the predominant asexual stage in the peripheral circulation but are rarely investigated in the context of acquired immunity against Plasmodium falciparum malaria. Here we compare antibody-dependent phagocytosis of ring-infected parasite cultures in samples from a contr...
MalariaPredictive markers
10.1038/S41467-022-31640-6
ISSN:2041-1723
Spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival
Duhamel Marie•Drelich Lauranne•Wisztorski Maxence•Aboulouard Soulaimane•Gimeno Jean-Pascal等 15 人
Nature Communications
2022
•2022/11/4
•Vol.13 No.1 p.1-16
Molecular heterogeneity is a key feature of glioblastoma that impedes patient stratification and leads to large discrepancies in mean patient survival. Here, we analyze a cohort of 96 glioblastoma patients with survival ranging from a few months to over 4 years. 46 tumors are analyzed by mass spectr...
CNS cancerTumour biomarkersTumour heterogeneity
10.1038/S41467-022-34208-6
ISSN:2041-1723
Connecting multiple microenvironment proteomes uncovers the biology in head and neck cancer
Busso-Lopes Ariane F.•Neves Leandro X.•Câmara Guilherme A.•Granato Daniela C.•Pretti Marco Antônio M.等 33 人
Nature Communications
2022
•2022/11/7
•Vol.13 No.1 p.1-24
The poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the ...
Head and neck cancerMetastasisPrognostic markersProteomicsTumour biomarkers
10.1038/S41467-022-34407-1
ISSN:2041-1723
A unique class of Zn2+-binding serine-based PBPs underlies cephalosporin resistance and sporogenesis in Clostridioides difficile
Sacco Michael D.•Wang Shaohui•Adapa Swamy R.•Zhang Xiujun•Lewandowski Eric M.等 19 人
Nature Communications
2022
•2022/7/28
•Vol.13 No.1 p.1-13
Treatment with β-lactam antibiotics, particularly cephalosporins, is a major risk factor for Clostridioides difficile infection. These broad-spectrum antibiotics irreversibly inhibit penicillin-binding proteins (PBPs), which are serine-based enzymes that assemble the bacterial cell wall. However, C....
Antimicrobial resistanceBacteriologyPathogensX-ray crystallography
10.1038/S41467-022-32086-6
ISSN:2041-1723
Bacterial pathogens deliver water- and solute-permeable channels to plant cells
Kinya Nomura•Felipe Andreazza•Jie Cheng•Ke Dong•Pei Zhou等 6 人
Nature
2023
•2023/9/13
•00 p.1-6
Many animal- and plant-pathogenic bacteria use a type III secretion system to deliver effector proteins into host cells1,2. Elucidation of how these effector proteins function in host cells is critical for understanding infectious diseases in animals and plants3–5. The widely conserved AvrE-family e...
Bacterial pathogenesisEffectors in plant pathology
10.1038/S41586-023-06531-5
ISSN:0028-0836
KK-LC-1 as a therapeutic target to eliminate ALDH+ stem cells in triple negative breast cancer
Bu Jiawen•Zhang Yixiao•Wu Sijin•Li Haonan•Sun Lisha等 15 人
Nature Communications
2023
•2023/5/5
•Vol.14 No.1 p.1-18
Failure to achieve complete elimination of triple negative breast cancer (TNBC) stem cells after adjuvant therapy is associated with poor outcomes. Aldehyde dehydrogenase 1 (ALDH1) is a marker of breast cancer stem cells (BCSCs), and its enzymatic activity regulates tumor stemness. Identifying upstr...
Breast cancerCancer stem cellsDrug discovery
10.1038/S41467-023-38097-1
ISSN:2041-1723
Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes
Bhardwaj Taniya•Gadhave Kundlik•Kapuganti Shivani K.•Kumar Prateek•Brotzakis Zacharias Faidon等 15 人
Nature Communications
2023
•2023/2/20
•Vol.14 No.1 p.1-16
The phenomenon of protein aggregation is associated with a wide range of human diseases. Our knowledge of the aggregation behaviour of viral proteins, however, is still rather limited. Here, we investigated this behaviour in the SARS-CoV and SARS-CoV-2 proteomes. An initial analysis using a panel of...
Atomic force microscopyProtein aggregationViral infection
10.1038/S41467-023-36234-4
ISSN:2041-1723
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
Profiling cell envelope-antibiotic interactions reveals vulnerabilities to β-lactams in a multidrug-resistant bacterium
Andrew M. Hogan•A. S. M. Zisanur Rahman•Anna Motnenko•Aakash Natarajan•Dustin T. Maydaniuk等 10 人
Nature Communications
2023
•2023/8/9
•Vol.14 No.1 p.1-21
The cell envelope of Gram-negative bacteria belonging to the Burkholderia cepacia complex (Bcc) presents unique restrictions to antibiotic penetration. As a consequence, Bcc species are notorious for causing recalcitrant multidrug-resistant infections in immunocompromised individuals. Here, we prese...
AntibioticsAntimicrobial resistanceBacteriaPathogens
10.1038/S41467-023-40494-5
ISSN:2041-1723
CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity
Long Lingyun•Wei Jun•Lim Seon Ah•Raynor Jana L.•Shi Hao等 27 人
Nature
2021
•2021/11/18
•00 p.1-6
Nutrients are emerging regulators of adaptive immunity1. Selective nutrients interplay with immunological signals to activate mechanistic target of rapamycin complex 1 (mTORC1), a key driver of cell metabolism2–4, but how these environmental signals are integrated for immune regulation remains uncle...
CD4-positive T cellsSignal transduction
10.1038/S41586-021-04109-7
ISSN:0028-0836
A tissue-specific atlas of protein–protein associations enables prioritization of candidate disease genes
Diederik S. Laman Trip•Marc van Oostrum•Danish Memon•Fabian Frommelt•Delora Baptista等 17 人
Nature Biotechnology
2025
•2025/5/2
•00 p.1-14
Despite progress in mapping protein–protein interactions, their tissue specificity is understudied. Here, given that protein coabundance is predictive of functional association, we compiled and analyzed protein abundance data of 7,811 proteomic samples from 11 human tissues to produce an atlas of ti...
Computational biology and bioinformaticsProteomic analysisTarget identification
10.1038/S41587-025-02659-Z
ISSN:1087-0156
VWCE modulates amino acid-dependent mTOR signaling and coordinates with KICSTOR to recruit GATOR1 to the lysosomes
Tianyu Zhao•Yuanyuan Guan•Chenchen Xu•Dong Wang•Jialiang Guan等 6 人
Nature Communications
2023
•2023/12/20
•Vol.14 No.1 p.1-10
The mechanistic target of rapamycin complex 1 (mTORC1) is a crucial regulator of cell growth. It senses nutrient signals and adjusts cellular metabolism accordingly. Deregulation of mTORC1 has been associated with metabolic diseases, cancer, and aging. Amino acid signals are transduced to mTORC1 thr...
LysosomesNutrient signallingTOR signalling
10.1038/S41467-023-44241-8
ISSN:2041-1723
Rational correction of pathogenic conformational defects in HTRA1
Nathalie Beaufort•Linda Ingendahl•Melisa Merdanovic•Andree Schmidt•David Podlesainski等 38 人
Nature Communications
2024
•2024/7/16
•Vol.15 No.1 p.1-18
Loss-of-function mutations in the homotrimeric serine protease HTRA1 cause cerebral vasculopathy. Here, we establish independent approaches to achieve the functional correction of trimer assembly defects. Focusing on the prototypical R274Q mutation, we identify an HTRA1 variant that promotes trimer ...
BiologicsNMR spectroscopyProteasesProteomics
10.1038/S41467-024-49982-8
ISSN:2041-1723
53BP1–shieldin-dependent DSB processing in BRCA1-deficient cells requires CST–Polα–primase fill-in synthesis
Mirman Zachary•Sasi Nanda Kumar•King Ashleigh•Chapman J. Ross•de Lange Titia
Nature Cell Biology
2022
•2022/1/13
•00 p.1-11
The efficacy of poly(ADP)-ribose polymerase 1 inhibition (PARPi) in BRCA1-deficient cells depends on 53BP1 and shieldin, which have been proposed to limit single-stranded DNA at double-strand breaks (DSBs) by blocking resection and/or through CST–Polα–primase-mediated fill-in. We show that primase (...
DNA damage responseDouble-strand DNA breaksNon-homologous-end joining
10.1038/S41556-021-00812-9
ISSN:1465-7392
Gut microbial-derived phenylacetylglutamine accelerates host cellular senescence
Hao Yang•Tongyao Wang•Chenglang Qian•Huijing Wang•Dong Yu等 27 人
Nature Aging
2025
•2025/1/10
•00 p.1-18
Gut microbiota plays a crucial role in the host health in the aging process. However, the mechanisms for how gut microbiota triggers cellular senescence and the consequent impact on human aging remain enigmatic. Here we show that phenylacetylglutamine (PAGln), a metabolite linked to gut microbiota, ...
AgeingMedical researchMicrobiologySenescence
10.1038/S43587-024-00795-W
ISSN:2662-8465
Mitochondrial complexome reveals quality-control pathways of protein import
Schulte Uwe•den Brave Fabian•Haupt Alexander•Gupta Arushi•Song Jiyao等 20 人
Nature
2023
•2023/1/25
•Vol.614 No.7946 p.153-159
Mitochondria have crucial roles in cellular energetics, metabolism, signalling and quality control1–4. They contain around 1,000 different proteins that often assemble into complexes and supercomplexes such as respiratory complexes and preprotein translocases1,3–7. The composition of the mitochondri...
MitochondriaProtein–protein interaction networksProtein translocation
10.1038/S41586-022-05641-W
ISSN:0028-0836
Hologenome analysis reveals dual symbiosis in the deep-sea hydrothermal vent snail Gigantopelta aegis
Yi Lan•Jin Sun•Chong Chen•Yanan Sun•Yadong Zhou等 16 人
Nature Communications
2021
•2021/2/19
•Vol.12 No.1 p.1-15
Animals endemic to deep-sea hydrothermal vents often form obligatory symbioses with bacteria, maintained by intricate host–symbiont interactions. Most genomic studies on holobionts have not investigated both sides to similar depths. Here, we report dual symbiosis in the peltospirid snail Gigantopelt...
Bacterial genomicsGenomicsSymbiosis
10.1038/S41467-021-21450-7
ISSN:2041-1723
Identification of LTBP-2 as a plasma biomarker for right ventricular dysfunction in human pulmonary arterial hypertension
Boucherat Olivier•Yokokawa Tetsuro•Krishna Vinod•Kalyana-Sundaram Shanker•Martineau Sandra等 14 人
Nature Cardiovascular Research
2022
•2022/8/11
•Vol.1 No.8 p.748-760
Although right ventricular (RV) function is the primary determinant of morbidity and mortality in pulmonary arterial hypertension (PAH), the molecular mechanisms of RV remodeling and the circulating factors reflecting its function remain largely elusive. In this context, the identification of new mo...
Cardiac hypertrophyPrognostic markers
10.1038/S44161-022-00113-W
ISSN:2731-0590
Rapid, deep and precise profiling of the plasma proteome with multi-nanoparticle protein corona
John E. Blume•William C. Manning•Gregory Troiano•Daniel Hornburg•Michael Figa等 25 人
Nature Communications
2020
•2020/7/22
•Vol.11 No.1 p.1-14
Large-scale, unbiased proteomics studies are constrained by the complexity of the plasma proteome. Here we report a highly parallel protein quantitation platform integrating nanoparticle (NP) protein coronas with liquid chromatography-mass spectrometry for efficient proteomic profiling. A protein co...
Blood proteinsMass spectrometryNanoparticlesNon-small-cell lung cancerProteomics
10.1038/S41467-020-17033-7
ISSN:2041-1723
Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension
Rinschen Markus M.•Palygin Oleg•El-Meanawy Ashraf•Domingo-Almenara Xavier•Palermo Amelia等 25 人
Nature Communications
2022
•2022/7/14
•Vol.13 No.1 p.1-17
Hypertension and kidney disease have been repeatedly associated with genomic variants and alterations of lysine metabolism. Here, we combined stable isotope labeling with untargeted metabolomics to investigate lysine’s metabolic fate in vivo. Dietary 13C6 labeled lysine was tracked to lysine metabol...
KidneyMetabolomics
10.1038/S41467-022-31670-0
ISSN:2041-1723
Spatially resolved protein map of intact human cytomegalovirus virions
Boris Bogdanow•Iris Gruska•Lars Mühlberg•Jonas Protze•Svea Hohensee等 11 人
Nature Microbiology
2023
•2023/8/7
•00 p.1-16
Herpesviruses assemble large enveloped particles that are difficult to characterize structurally due to their size, fragility and complex multilayered proteome with partially amorphous nature. Here we used crosslinking mass spectrometry and quantitative proteomics to derive a spatially resolved inte...
Herpes virusSystems analysis
10.1038/S41564-023-01433-8
ISSN:2058-5276
PLM-interact: extending protein language models to predict protein-protein interactions
Dan Liu•Francesca Young•Kieran D. Lamb•Adalberto Claudio Quiros•Alexandrina Pancheva等 9 人
Nature Communications
2025
•2025/10/27
•Vol.16 No.1 p.1-14
Computational prediction of protein structure from amino acid sequence alone has been achieved with unprecedented accuracy, yet the prediction of protein-protein interactions remains a challenge. Here, we assess the ability of protein language models (PLMs), routinely applied to protein folding, to ...
Computational modelsMachine learningProtein designProtein function predictionsProtein structure predictions
10.1038/S41467-025-64512-W
ISSN:2041-1723
Two zinc finger proteins with functions in m6A writing interact with HAKAI
Zhang Mi•Bodi Zsuzsanna•Mackinnon Katarzyna•Zhong Silin•Archer Nathan等 8 人
Nature Communications
2022
•2022/3/2
•Vol.13 No.1 p.1-15
The methyltransferase complex (m6A writer), which catalyzes the deposition of N6-methyladenosine (m6A) in mRNAs, is highly conserved across most eukaryotic organisms, but its components and interactions between them are still far from fully understood. Here, using in vivo interaction proteomics, two...
Plant developmentPlant molecular biologyRNA modification
10.1038/S41467-022-28753-3
ISSN:2041-1723
Deep learning reveals antimicrobial peptides within prions
Marcelo D. T. Torres•Fangping Wan•Cesar de la Fuente-Nunez
Nature Microbiology
2026
•2026/6/19
•00 p.1-7
Prion and prion-like proteins are classically associated with protein misfolding, but amyloidogenic sequences can also participate in host defence. Here, using deep learning, we screened 19.3 million fragments from 2,897 curated prion-related proteins and identified 1,179 candidate antimicrobial pep...
AntimicrobialsMicrobiology
10.1038/S41564-026-02408-1
ISSN:2058-5276
BRCA1 binds TERRA RNA and suppresses R-Loop-based telomeric DNA damage
Jekaterina Vohhodina•Liana J. Goehring•Ben Liu•Qing Kong•Vladimir V. Botchkarev Jr.等 13 人
Nature Communications
2021
•2021/6/10
•Vol.12 No.1 p.1-16
R-loop structures act as modulators of physiological processes such as transcription termination, gene regulation, and DNA repair. However, they can cause transcription-replication conflicts and give rise to genomic instability, particularly at telomeres, which are prone to forming DNA secondary str...
ChromatinFragile sitesGenomic instabilityLong non-coding RNAsTelomeres
10.1038/S41467-021-23716-6
ISSN:2041-1723
Engineered platelets as targeted protein degraders and application to breast cancer models
Yu Chen•Samira Pal•Wen Li•Fengyuan Liu•Sichen Yuan等 6 人
Nature Biotechnology
2024
•2024/12/3
•00 p.1-13
Clinical application of chimeric molecules for targeted protein degradation has been limited by unfavorable drug-like properties and biosafety concerns arising from nonspecific biodistribution after systemic administration. Here we develop a method to engineer platelets for degradation of either int...
Biomedical engineeringDrug delivery
10.1038/S41587-024-02494-8
ISSN:1087-0156
Perturbing proteomes at single residue resolution using base editing
Philippe C. Després•Alexandre K. Dubé•Motoaki Seki•Nozomu Yachie•Christian R. Landry
Nature Communications
2020
•2020/4/20
•Vol.11 No.1 p.1-13
Base editors derived from CRISPR-Cas9 systems and DNA editing enzymes offer an unprecedented opportunity for the precise modification of genes, but have yet to be used at a genome-scale throughput. Here, we test the ability of the Target-AID base editor to systematically modify genes genome-wide by ...
CRISPR-Cas9 genome editingHigh-throughput screeningSynthetic biology
10.1038/S41467-020-15796-7
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
Functionally constrained human proteins are less prone to mutational instability from single amino acid substitutions
Maryam May•Aaron Chuah•Nicole Lehmann•Llewelyn Goodall•Vicky Cho等 6 人
Nature Communications
2025
•2025/3/13
•Vol.16 No.1 p.1-11
Missense mutations that disrupt protein structural stability are a common pathogenic mechanism in human genetic disease. Here, we quantify potential disruption of protein stability due to amino acid substitution and show that functionally constrained proteins are less susceptible to large mutational...
Genome informaticsMutationStructural biology
10.1038/S41467-025-57757-Y
ISSN:2041-1723
MFSD1 with its accessory subunit GLMP functions as a general dipeptide uniporter in lysosomes
Katharina Esther Julia Jungnickel•Océane Guelle•Miharu Iguchi•Wentao Dong•Vadim Kotov等 20 人
Nature Cell Biology
2024
•2024/6/5
•00 p.1-15
The lysosomal degradation of macromolecules produces diverse small metabolites exported by specific transporters for reuse in biosynthetic pathways. Here we deorphanized the major facilitator superfamily domain containing 1 (MFSD1) protein, which forms a tight complex with the glycosylated lysosomal...
BiochemistryCryoelectron microscopyLysosomesMetabolomics
10.1038/S41556-024-01436-5
ISSN:1465-7392
Improved measures for evolutionary conservation that exploit taxonomy distances
Nawar Malhis•Steven J. M. Jones•Jörg Gsponer
Nature Communications
2019
•2019/4/5
•Vol.10 No.1 p.1-8
Selective pressures on protein-coding regions that provide fitness advantages can lead to the regions' fixation and conservation in genome duplications and speciation events. Consequently, conservation analyses relying on sequence similarities are exploited by a myriad of applications across all bio...
Computational biology and bioinformaticsGeneticsMolecular evolution
10.1038/S41467-019-09583-2
ISSN:2041-1723
Molecular basis for the catalytic mechanism of human neutral sphingomyelinases 1 (hSMPD2)
Jingbo Yi•Boya Qi•Jian Yin•Ruochong Li•Xudong Chen等 10 人
Nature Communications
2023
•2023/11/27
•Vol.14 No.1 p.1-13
Enzymatic breakdown of sphingomyelin by sphingomyelinase (SMase) is the main source of the membrane lipids, ceramides, which are involved in many cellular physiological processes. However, the full-length structure of human neutral SMase has not been resolved; therefore, its catalytic mechanism rema...
Cryoelectron microscopyEnzyme mechanismsHydrolases
10.1038/S41467-023-43580-W
ISSN:2041-1723
Decreased spliceosome fidelity and egl-8 intron retention inhibit mTORC1 signaling to promote longevity
Huang Wenming•Kew Chun•Fernandes Stephanie de Alcantara•Löhrke Anna•Han Lynn等 7 人
Nature Aging
2022
•2022/9/19
•Vol.2 No.9 p.796-808
Changes in splicing fidelity are associated with loss of homeostasis and aging, yet only a handful of splicing factors have been shown to be causally required to promote longevity, and the underlying mechanisms and downstream targets in these paradigms remain elusive. Surprisingly, we found a hypomo...
AgeingCell signallingRNA splicing
10.1038/S43587-022-00275-Z
ISSN:2662-8465
DHX9 SUMOylation is required for the suppression of R-loop-associated genome instability
Bing-Ze Yang•Mei-Yin Liu•Kuan-Lin Chiu•Yuh-Ling Chien•Ching-An Cheng等 10 人
Nature Communications
2024
•2024/7/17
•Vol.15 No.1 p.1-18
RNA helicase DHX9 is essential for genome stability by resolving aberrant R-loops. However, its regulatory mechanisms remain unclear. Here we show that SUMOylation at lysine 120 (K120) is crucial for DHX9 function. Preventing SUMOylation at K120 leads to R-loop dysregulation, increased DNA damage, a...
DNA damage and repairRNASumoylation
10.1038/S41467-024-50428-4
ISSN:2041-1723
Paradoxical activation of the protein kinase-transcription factor ERK5 by ERK5 kinase inhibitors
Pamela A. Lochhead•Julie A. Tucker•Natalie J. Tatum•Jinhua Wang•David Oxley等 11 人
Nature Communications
2020
•2020/3/13
•Vol.11 No.1 p.1-16
The dual protein kinase-transcription factor, ERK5, is an emerging drug target in cancer and inflammation, and small-molecule ERK5 kinase inhibitors have been developed. However, selective ERK5 kinase inhibitors fail to recapitulate ERK5 genetic ablation phenotypes, suggesting kinase-independent fun...
BiochemistryCancerCell signallingCellular imagingEnzyme mechanisms
10.1038/S41467-020-15031-3
ISSN:2041-1723
Expansion within the CYP71D subfamily drives the heterocyclization of tanshinones synthesis in Salvia miltiorrhiza
Ying Ma•Guanghong Cui•Tong Chen•Xiaohui Ma•Ruishan Wang等 18 人
Nature Communications
2021
•2021/1/29
•Vol.12 No.1 p.1-11
Tanshinones are the bioactive nor-diterpenoid constituents of the Chinese medicinal herb Danshen (Salvia miltiorrhiza). These groups of chemicals have the characteristic furan D-ring, which differentiates them from the phenolic abietane-type diterpenoids frequently found in the Lamiaceae family. How...
GenomicsPlant evolutionSecondary metabolism
10.1038/S41467-021-20959-1
ISSN:2041-1723
An exported kinase family mediates species-specific erythrocyte remodelling and virulence in human malaria
Heledd Davies•Hugo Belda•Malgorzata Broncel•Xingda Ye•Claudine Bisson等 12 人
Nature Microbiology
2020
•2020/4/13
•Vol.5 No.6 p.848-863
The most severe form of human malaria is caused by Plasmodium falciparum. Its virulence is closely linked to the increase in rigidity of infected erythrocytes and their adhesion to endothelial receptors, obstructing blood flow to vital organs. Unlike other human-infecting Plasmodium species, P. falc...
KinasesMechanisms of diseaseParasite biologyParasite host responsePhosphorylation
10.1038/S41564-020-0702-4
ISSN:2058-5276
Entropy of a bacterial stress response is a generalizable predictor for fitness and antibiotic sensitivity
Zeyu Zhu•Defne Surujon•Juan C. Ortiz-Marquez•Wenwen Huo•Ralph R. Isberg等 7 人
Nature Communications
2020
•2020/8/31
•Vol.11 No.1 p.1-15
Current approaches explore bacterial genes that change transcriptionally upon stress exposure as diagnostics to predict antibiotic sensitivity. However, transcriptional changes are often specific to a species or antibiotic, limiting implementation to known settings only. While a generalizable approa...
Antibacterial drug resistanceAntimicrobial resistanceBacterial systems biologySystems biology
10.1038/S41467-020-18134-Z
ISSN:2041-1723
Heritable microbiome variation is correlated with source environment in locally adapted maize varieties
Xiaoming He•Danning Wang•Yong Jiang•Meng Li•Manuel Delgado-Baquerizo等 27 人
Nature Plants
2024
•2024/3/21
•00 p.1-20
Beneficial interactions with microorganisms are pivotal for crop performance and resilience. However, it remains unclear how heritable the microbiome is with respect to the host plant genotype and to what extent host genetic mechanisms can modulate plant–microbiota interactions in the face of enviro...
AbioticPlant developmentPlant genetics
10.1038/S41477-024-01654-7
ISSN:2055-0278
Phosphoproteome profiling uncovers a key role for CDKs in TNF signaling
Tanzer Maria C.•Bludau Isabell•Stafford Che A.•Hornung Veit•Mann Matthias
Nature Communications
2021
•2021/10/18
•Vol.12 No.1 p.1-15
Tumor necrosis factor (TNF) is one of the few cytokines successfully targeted by therapies against inflammatory diseases. However, blocking this well studied and pleiotropic ligand can cause dramatic side-effects. Here, we reason that a systems-level proteomic analysis of TNF signaling could dissect...
Cell death and immune responsePhosphorylationProteomicsTumour-necrosis factors
10.1038/S41467-021-26289-6
ISSN:2041-1723
Guidance landscapes unveiled by quantitative proteomics to control reinnervation in adult visual system
Vilallongue Noemie•Schaeffer Julia•Hesse Anne-Marie•Delpech Céline•Blot Béatrice等 11 人
Nature Communications
2022
•2022/10/13
•Vol.13 No.1 p.1-20
In the injured adult central nervous system (CNS), activation of pro-growth molecular pathways in neurons leads to long-distance regeneration. However, most regenerative fibers display guidance defects, which prevent reinnervation and functional recovery. Therefore, the molecular characterization of...
Neural circuitsProteomicsRegeneration and repair in the nervous systemVisual system
10.1038/S41467-022-33799-4
ISSN:2041-1723
The Akt/mTOR and MNK/eIF4E pathways rewire the prostate cancer translatome to secrete HGF, SPP1 and BGN and recruit suppressive myeloid cells
Daniela Brina•Adele Ponzoni•Martina Troiani•Bianca Calì•Emiliano Pasquini等 39 人
Nature Cancer
2023
•2023/7/17
•00 p.1-20
Cancer is highly infiltrated by myeloid-derived suppressor cells (MDSCs). Currently available immunotherapies do not completely eradicate MDSCs. Through a genome-wide analysis of the translatome of prostate cancers driven by different genetic alterations, we demonstrate that prostate cancer rewires ...
CancerCancer immunotherapyProstate cancerTumour immunology
10.1038/S43018-023-00594-Z
ISSN:2662-1347
EMC rectifies the topology of multipass membrane proteins
Haoxi Wu•Luka Smalinskaitė•Ramanujan S. Hegde
Nature Structural & Molecular Biology
2023
•2023/11/13
•00 p.1-10
Most eukaryotic multipass membrane proteins are inserted into the membrane of the endoplasmic reticulum. Their transmembrane domains (TMDs) are thought to be inserted co-translationally as they emerge from a membrane-bound ribosome. Here we find that TMDs near the carboxyl terminus of mammalian mult...
Endoplasmic reticulumMembrane proteins
10.1038/S41594-023-01120-6
ISSN:1545-9993
Efficient evolution of human antibodies from general protein language models
Hie Brian L.•Shanker Varun R.•Xu Duo•Bruun Theodora U. J.•Weidenbacher Payton A.等 9 人
Nature Biotechnology
2023
•2023/4/24
•00 p.1-9
Natural evolution must explore a vast landscape of possible sequences for desirable yet rare mutations, suggesting that learning from natural evolutionary strategies could guide artificial evolution. Here we report that general protein language models can efficiently evolve human antibodies by sugge...
Drug discoveryMachine learningMolecular evolution
10.1038/S41587-023-01763-2
ISSN:1087-0156
Urinary Complement proteome strongly linked to diabetic kidney disease progression
Zaipul I. Md Dom•Salina Moon•Eiichiro Satake•Daigoro Hirohama•Nicholette D. Palmer等 21 人
Nature Communications
2025
•2025/8/7
•Vol.16 No.1 p.1-19
Diabetic kidney disease (DKD) progression is not well understood. Using high-throughput proteomics, biostatistical, pathway and machine learning tools, we examine the urinary Complement proteome in two prospective cohorts with type 1 or 2 diabetes and advanced DKD followed for 1,804 person-years. Th...
Chronic kidney diseaseData miningPrognostic markersProteomics
10.1038/S41467-025-62101-5
ISSN:2041-1723
Proteomics of resistance to Notch1 inhibition in acute lymphoblastic leukemia reveals targetable kinase signatures
Giulia Franciosa•Jos G. A. Smits•Sonia Minuzzo•Ana Martinez-Val•Stefano Indraccolo等 6 人
Nature Communications
2021
•2021/5/4
•Vol.12 No.1 p.1-19
Notch1 is a crucial oncogenic driver in T-cell acute lymphoblastic leukemia (T-ALL), making it an attractive therapeutic target. However, the success of targeted therapy using γ-secretase inhibitors (GSIs), small molecules blocking Notch cleavage and subsequent activation, has been limited due to de...
Acute lymphocytic leukaemiaCell signallingMass spectrometryProteomics
10.1038/S41467-021-22787-9
ISSN:2041-1723
Graph pangenome captures missing heritability and empowers tomato breeding
Zhou Yao•Zhang Zhiyang•Bao Zhigui•Li Hongbo•Lyu Yaqing等 22 人
Nature
2022
•2022/6/8
•Vol.606 No.7914 p.527-534
Missing heritability in genome-wide association studies defines a major problem in genetic analyses of complex biological traits1,2. The solution to this problem is to identify all causal genetic variants and to measure their individual contributions3,4. Here we report a graph pangenome of tomato co...
Agricultural geneticsGenome-wide association studiesGenomicsPlant breedingStructural variation
10.1038/S41586-022-04808-9
ISSN:0028-0836
RNF43 G659fs is an oncogenic colorectal cancer mutation and sensitizes tumor cells to PI3K/mTOR inhibition
Fang Lishan•Ford-Roshon Dane•Russo Max•O’Brien Casey•Xiong Xiaozhe等 15 人
Nature Communications
2022
•2022/6/8
•Vol.13 No.1 p.1-12
The RNF43_p.G659fs mutation occurs frequently in colorectal cancer, but its function remains poorly understood and there are no specific therapies directed against this alteration. In this study, we find that RNF43_p.G659fs promotes cell growth independent of Wnt signaling. We perform a drug repurpo...
Colorectal cancerMolecular biology
10.1038/S41467-022-30794-7
ISSN:2041-1723
Immunopeptidomics-based design of mRNA vaccine formulations against Listeria monocytogenes
Mayer Rupert L.•Verbeke Rein•Asselman Caroline•Aernout Ilke•Gul Adillah等 17 人
Nature Communications
2022
•2022/10/14
•Vol.13 No.1 p.1-17
Listeria monocytogenes is a foodborne intracellular bacterial pathogen leading to human listeriosis. Despite a high mortality rate and increasing antibiotic resistance no clinically approved vaccine against Listeria is available. Attenuated Listeria strains offer protection and are tested as antitum...
ListeriaProteomicsVaccines
10.1038/S41467-022-33721-Y
ISSN:2041-1723
Cross-regulation of viral kinases with cyclin A secures shutoff of host DNA synthesis
Boris Bogdanow•Max Schmidt•Henry Weisbach•Iris Gruska•Barbara Vetter等 11 人
Nature Communications
2020
•2020/9/24
•Vol.11 No.1 p.1-13
Herpesviruses encode conserved protein kinases (CHPKs) to stimulate phosphorylation-sensitive processes during infection. How CHPKs bind to cellular factors and how this impacts their regulatory functions is poorly understood. Here, we use quantitative proteomics to determine cellular interaction pa...
DNA synthesisHerpes virusKinasesMass spectrometryProtein–protein interaction networks
10.1038/S41467-020-18542-1
ISSN:2041-1723
Light-mediated discovery of surfaceome nanoscale organization and intercellular receptor interaction networks
Müller Maik•Gräbnitz Fabienne•Barandun Niculò•Shen Yang•Wendt Fabian等 21 人
Nature Communications
2021
•2021/12/2
•Vol.12 No.1 p.1-17
The molecular nanoscale organization of the surfaceome is a fundamental regulator of cellular signaling in health and disease. Technologies for mapping the spatial relationships of cell surface receptors and their extracellular signaling synapses would unlock theranostic opportunities to target prot...
Chemical toolsExtracellular signalling moleculesProtein–protein interaction networksTarget identification
10.1038/S41467-021-27280-X
ISSN:2041-1723
pGlycoQuant with a deep residual network for quantitative glycoproteomics at intact glycopeptide level
Kong Siyuan•Gong Pengyun•Zeng Wen-Feng•Jiang Biyun•Hou Xinhang等 15 人
Nature Communications
2022
•2022/12/7
•Vol.13 No.1 p.1-17
Large-scale intact glycopeptide identification has been advanced by software tools. However, tools for quantitative analysis remain lagging behind, which hinders exploring the differential site-specific glycosylation. Here, we report pGlycoQuant, a generic tool for both primary and tandem mass spect...
GlycobiologyMass spectrometryProteome informaticsProteomics
10.1038/S41467-022-35172-X
ISSN:2041-1723
A translational program that suppresses metabolism to shield the genome
Nathan C. Balukoff•J. J. David Ho•Phaedra R. Theodoridis•Miling Wang•Michael Bokros等 9 人
Nature Communications
2020
•2020/11/13
•Vol.11 No.1 p.1-15
Translatome reprogramming is a primary determinant of protein levels during stimuli adaptation. This raises the question: what are the translatome remodelers that reprogram protein output to activate biochemical adaptations. Here, we identify a translational pathway that represses metabolism to safe...
Systems biologyTranslation
10.1038/S41467-020-19602-2
ISSN:2041-1723
Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance
Yu Jason S. L.•Correia-Melo Clara•Zorrilla Francisco•Herrera-Dominguez Lucia•Wu Mary Y.等 19 人
Nature Microbiology
2022
•2022/3/21
•00 p.1-14
Microbial communities are composed of cells of varying metabolic capacity, and regularly include auxotrophs that lack essential metabolic pathways. Through analysis of auxotrophs for amino acid biosynthesis pathways in microbiome data derived from >12,000 natural microbial communities obtained as...
AntimicrobialsMicrobial ecology
10.1038/S41564-022-01072-5
ISSN:2058-5276
Cryo-EM structures of engineered active bc 1 - cbb 3 type CIII 2 CIV super-complexes and electronic communication between the complexes
Stefan Steimle•Trevor van Eeuwen•Yavuz Ozturk•Hee Jong Kim•Merav Braitbard等 10 人
Nature Communications
2021
•2021/2/10
•Vol.12 No.1 p.1-14
Respiratory electron transport complexes are organized as individual entities or combined as large supercomplexes (SC). Gram-negative bacteria deploy a mitochondrial-like cytochrome (cyt) bc1 (Complex III, CIII2), and may have specific cbb3-type cyt c oxidases (Complex IV, CIV) instead of the canoni...
Cryoelectron microscopyMembrane proteinsMultienzyme complexesRespiration
10.1038/S41467-021-21051-4
ISSN:2041-1723
Export of defensive glucosinolates is key for their accumulation in seeds
Xu Deyang•Sanden Niels Christian Holm•Hansen Line Lykke•Belew Zeinu Mussa•Madsen Svend Roesen等 13 人
Nature
2023
•2023/4/19
•00 p.1-7
Plant membrane transporters controlling metabolite distribution contribute key agronomic traits1–6. To eliminate anti-nutritional factors in edible parts of crops, the mutation of importers can block the accumulation of these factors in sink tissues7. However, this often results in a substantially a...
Molecular engineering in plantsPlant immunityPlant transportersSecondary metabolism
10.1038/S41586-023-05969-X
ISSN:0028-0836
In vivo endosomal escape assay identifies mechanisms for efficient hepatic LNP delivery
Antony Jozić•Chloé Le Roux•Jeonghwan Kim•Mathieu Berchel•Deepak Kumar Sahel等 15 人
Nature Biotechnology
2026
•2026/3/11
•00 p.1-11
Endosomal escape is a central barrier to efficient nucleic acid delivery by lipid nanoparticles (LNPs) and remains challenging to quantify in vivo. We report a library of branched ionizable phospholipids that markedly enhance messenger RNA delivery to the liver. The lead candidate BiP-20 outperforme...
Gene therapyNanoparticlesProteomics
10.1038/S41587-026-03022-6
ISSN:1087-0156
Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants
Sanders Bret•D’Andrea Daniel•Collins Mark O.•Rees Elliott•Steward Tom G. J.等 18 人
Nature Communications
2022
•2022/1/14
•Vol.13 No.1 p.1-21
Coordinated programs of gene expression drive brain development. It is unclear which transcriptional programs, in which cell-types, are affected in neuropsychiatric disorders such as schizophrenia. Here we integrate human genetics with transcriptomic data from differentiation of human embryonic stem...
Developmental neurogenesisSchizophreniaStem-cell differentiationTranscriptomics
10.1038/S41467-021-27601-0
ISSN:2041-1723
A unified evolution-driven deep learning framework for virus variation driver prediction
Zhiwei Nie•Xudong Liu•Jie Chen•Zhennan Wang•Yutian Liu等 13 人
Nature Machine Intelligence
2025
•2025/1/17
•00 p.1-14
The increasing frequency of emerging viral infections necessitates a rapid human response, highlighting the cost-effectiveness of computational methods. However, existing computational approaches are limited by their input forms or incomplete functionalities, preventing a unified prediction of diver...
Machine learningProtein function predictionsSARS-CoV-2
10.1038/S42256-024-00966-9
ISSN:2522-5839
A protein sequence-based deep transfer learning framework for identifying human proteome-wide deubiquitinase-substrate interactions
Yuan Liu•Dianke Li•Xin Zhang•Simin Xia•Yingjie Qu等 11 人
Nature Communications
2024
•2024/5/28
•Vol.15 No.1 p.1-16
Protein ubiquitination regulates a wide range of cellular processes. The degree of protein ubiquitination is determined by the delicate balance between ubiquitin ligase (E3)-mediated ubiquitination and deubiquitinase (DUB)-mediated deubiquitination. In comparison to the E3-substrate interactions, th...
Cellular signalling networksComputational modelsProteome informatics
10.1038/S41467-024-48446-3
ISSN:2041-1723
ZNF768 links oncogenic RAS to cellular senescence
Villot Romain•Poirier Audrey•Bakan Inan•Boulay Karine•Fernández Erlinda等 25 人
Nature Communications
2021
•2021/8/17
•Vol.12 No.1 p.1-15
RAS proteins are GTPases that lie upstream of a signaling network impacting cell fate determination. How cells integrate RAS activity to balance proliferation and cellular senescence is still incompletely characterized. Here, we identify ZNF768 as a phosphoprotein destabilized upon RAS activation. W...
CancerGrowth factor signallingSenescence
10.1038/S41467-021-24932-W
ISSN:2041-1723
Identifying nutraceutical targets to treat polycystic ovary syndrome using graph representation learning
Simon Hanassab•Joshua Southern•Ayomide V. Olabode•Ivan Laponogov•Michael Bronstein等 11 人
Npj Women's Health
2025
•2025/12/1
•Vol.3 No.1 p.680
Polycystic ovary syndrome (PCOS) is a complex, multifactorial, and polygenic disorder. Here, we employed machine learning (ML) techniques to analyze large open-source datasets to identify bioactive molecules in foods and pharmacological agents that interact with genes and biological functions centra...
Endocrine reproductive disordersReproductive biologyReproductive disorders
10.1038/S44294-025-00117-4
ISSN:2948-1716
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
Semantic design of functional de novo genes from a genomic language model
Aditi T. Merchant•Samuel H. King•Eric Nguyen•Brian L. Hie
Nature
2025
•2025/11/19
•00 p.1-10
Generative genomic models can design increasingly complex biological systems1. However, controlling these models to generate novel sequences with desired functions remains challenging. Here, we show that Evo, a genomic language model, can leverage genomic context to perform function-guided design th...
Computational modelsGenetic databasesMachine learningProtein design
10.1038/S41586-025-09749-7
ISSN:0028-0836
A complex of BRCA2 and PP2A-B56 is required for DNA repair by homologous recombination
Ambjørn Sara M.•Duxin Julien P.•Hertz Emil P. T.•Nasa Isha•Duro Joana等 14 人
Nature Communications
2021
•2021/9/30
•Vol.12 No.1 p.1-11
Mutations in the tumour suppressor gene BRCA2 are associated with predisposition to breast and ovarian cancers. BRCA2 has a central role in maintaining genome integrity by facilitating the repair of toxic DNA double-strand breaks (DSBs) by homologous recombination (HR). BRCA2 acts by controlling RAD...
DNA-binding proteinsPhosphorylation
10.1038/S41467-021-26079-0
ISSN:2041-1723
Identification of antimicrobial peptides from the human gut microbiome using deep learning
Ma Yue•Guo Zhengyan•Xia Binbin•Zhang Yuwei•Liu Xiaolin等 13 人
Nature Biotechnology
2022
•2022/3/3
•00 p.1-11
The human gut microbiome encodes a large variety of antimicrobial peptides (AMPs), but the short lengths of AMPs pose a challenge for computational prediction. Here we combined multiple natural language processing neural network models, including LSTM, Attention and BERT, to form a unified pipeline ...
AntibioticsDrug development
10.1038/S41587-022-01226-0
ISSN:1546-1696
Ecological genomics in the Northern krill uncovers loci for local adaptation across ocean basins
Per Unneberg•Mårten Larsson•Anna Olsson•Ola Wallerman•Anna Petri等 15 人
Nature Communications
2024
•2024/8/1
•Vol.15 No.1 p.1-29
Krill are vital as food for many marine animals but also impacted by global warming. To learn how they and other zooplankton may adapt to a warmer world we studied local adaptation in the widespread Northern krill (Meganyctiphanes norvegica). We assemble and characterize its large genome and compare...
Evolutionary ecologyEvolutionary geneticsGenetic variationGenome evolution
10.1038/S41467-024-50239-7
ISSN:2041-1723
The mammalian longevity associated acetylome
S. Feldman-Trabelsi•N. Touitou•R. Nagar•Z. Schwartz•A. Michelson等 10 人
Nature Communications
2025
•2025/4/22
•Vol.16 No.1 p.1-15
Despite extensive studies at the genomic, transcriptomic and metabolomic levels, the underlying mechanisms regulating longevity are incompletely understood. Post-translational protein acetylation is suggested to regulate aspects of longevity. To further explore the role of acetylation, we develop th...
AcetylationAgeingProteome informatics
10.1038/S41467-025-58762-X
ISSN:2041-1723
Reagentless biomolecular analysis using a molecular pendulum
Jagotamoy Das•Surath Gomis•Jenise B. Chen•Hanie Yousefi•Sharif Ahmed等 9 人
Nature Chemistry
2021
•2021/3/8
•00 p.1-7
The development of reagentless sensors that can detect molecular analytes in biological fluids could enable a broad range of applications in personalized health monitoring. However, only a limited set of molecular inputs can currently be detected using reagentless sensors. Here, we report a sensing ...
Bioanalytical chemistryBiosensorsSensors
10.1038/S41557-021-00644-Y
ISSN:1755-4330
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
Viral subversion of selective autophagy is critical for biogenesis of virus replication organelles
Yun Lan•Sophie Wilhelmina van Leur•Julia Ayano Fernando•Ho Him Wong•Martin Kampmann等 10 人
Nature Communications
2023
•2023/5/10
•Vol.14 No.1 p.1-15
Infection by many (+)RNA viruses is accompanied by ER-expansion and membrane remodelling to form viral replication organelles, followed by assembly and secretion of viral progenies. We previously identified that virus-triggered lipophagy was critical for flaviviral assembly, and is driven by the lip...
Endoplasmic reticulumInfectionViral infection
10.1038/S41467-023-38377-W
ISSN:2041-1723
NINJ1 mediates plasma membrane rupture during lytic cell death
Nobuhiko Kayagaki•Opher S. Kornfeld•Bettina L. Lee•Irma B. Stowe•Karen O’Rourke等 27 人
Nature
2021
•2021/1/20
•Vol.591 No.7848 p.131-136
Plasma membrane rupture (PMR) is the final cataclysmic event in lytic cell death. PMR releases intracellular molecules known as damage-associated molecular patterns (DAMPs) that propagate the inflammatory response1–3. The underlying mechanism of PMR, however, is unknown. Here we show that the cell-s...
ApoptosisInflammasome
10.1038/S41586-021-03218-7
ISSN:0028-0836
Assigning functionality to cysteines by base editing of cancer dependency genes
Haoxin Li•Tiantai Ma•Jarrett R. Remsberg•Sang Joon Won•Kristen E. DeMeester等 16 人
Nature Chemical Biology
2023
•2023/10/2
•00 p.1-11
Covalent chemistry represents an attractive strategy for expanding the ligandability of the proteome, and chemical proteomics has revealed numerous electrophile-reactive cysteines on diverse human proteins. Determining which of these covalent binding events affect protein function, however, remains ...
CancerChemical toolsGeneticsProteomics
10.1038/S41589-023-01428-W
ISSN:1552-4450
Deep learning the collisional cross sections of the peptide universe from a million experimental values
Florian Meier•Niklas D. Köhler•Andreas-David Brunner•Jean-Marc H. Wanka•Eugenia Voytik等 8 人
Nature Communications
2021
•2021/2/19
•Vol.12 No.1 p.1-12
The size and shape of peptide ions in the gas phase are an under-explored dimension for mass spectrometry-based proteomics. To investigate the nature and utility of the peptide collisional cross section (CCS) space, we measure more than a million data points from whole-proteome digests of five organ...
Machine learningMass spectrometryProteomics
10.1038/S41467-021-21352-8
ISSN:2041-1723
Rare phenotype: Hand preaxial polydactyly associated with LRP6-related tooth agenesis in humans
Zhang Liutao•Yu Miao•Sun Kai•Fan Zhuangzhuang•Liu Haochen等 8 人
Npj Genomic Medicine
2021
•2021/11/10
•Vol.6 No.1 p.1-8
Low-density lipoprotein receptor-related protein 6 (LRP6) is a pathogenic gene of selective tooth agenesis-7 (OMIM#616724). Although the malformation of the digits and fore- and hindlimbs has been reported in Lrp6-deficient mice, it has been rarely discovered in humans with LRP6 mutations. Here, we ...
Dental diseasesDisease genetics
10.1038/S41525-021-00262-0
ISSN:2056-7944
Combining mass spectrometry and machine learning to discover bioactive peptides
Madsen Christian T.•Refsgaard Jan C.•Teufel Felix G.•Kjærulff Sonny K.•Wang Zhe等 24 人
Nature Communications
2022
•2022/10/20
•Vol.13 No.1 p.1-17
Peptides play important roles in regulating biological processes and form the basis of a multiplicity of therapeutic drugs. To date, only about 300 peptides in human have confirmed bioactivity, although tens of thousands have been reported in the literature. The majority of these are inactive degrad...
Machine learningPeptidesProteomicsTarget identification
10.1038/S41467-022-34031-Z
ISSN:2041-1723
Human transcription factor protein interaction networks
Göös Helka•Kinnunen Matias•Salokas Kari•Tan Zenglai•Liu Xiaonan等 9 人
Nature Communications
2022
•2022/2/9
•Vol.13 No.1 p.1-16
Transcription factors (TFs) interact with several other proteins in the process of transcriptional regulation. Here, we identify 6703 and 1536 protein–protein interactions for 109 different human TFs through proximity-dependent biotinylation (BioID) and affinity purification mass spectrometry (AP-MS...
Protein–protein interaction networksRegulatory networksTranscription
10.1038/S41467-022-28341-5
ISSN:2041-1723
GproDIA enables data-independent acquisition glycoproteomics with comprehensive statistical control
Yang Yi•Yan Guoquan•Kong Siyuan•Wu Mengxi•Yang Pengyuan等 7 人
Nature Communications
2021
•2021/10/18
•Vol.12 No.1 p.1-15
Large-scale profiling of intact glycopeptides is critical but challenging in glycoproteomics. Data independent acquisition (DIA) is an emerging technology with deep proteome coverage and accurate quantitative capability in proteomics studies, but is still in the early stage of development in the fie...
GlycobiologyMass spectrometryProteome informaticsProteomics
10.1038/S41467-021-26246-3
ISSN:2041-1723
The fast-evolving FIKK kinase family of Plasmodium falciparum can be inhibited by a single compound
Hugo Belda•David Bradley•Evangelos Christodoulou•Stephanie D. Nofal•Malgorzata Broncel等 19 人
Nature Microbiology
2025
•2025/5/19
•00 p.1-21
Of 250 Plasmodium species, 6 infect humans, with P. falciparum causing over 95% of 600,000 annual malaria-related deaths. Its pathology arises from host cell remodelling driven by over 400 exported parasite proteins, including the FIKK kinase family. About one million years ago, a bird-infecting Pla...
KinasesMolecular evolutionParasite evolutionX-ray crystallography
10.1038/S41564-025-02017-4
ISSN:2058-5276
CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module
Gerard W. Dougherty•Katsutoshi Mizuno•Tabea Nöthe-Menchen•Yayoi Ikawa•Karsten Boldt等 51 人
Nature Communications
2020
•2020/11/2
•Vol.11 No.1 p.1-20
Axonemal dynein ATPases direct ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar beating is not fully understood. Here, we describe a deficiency of cilia and flagella associat...
DiseasesGenetics
10.1038/S41467-020-19113-0
ISSN:2041-1723
Antibiotic susceptibility signatures identify potential antimicrobial targets in the Acinetobacter baumannii cell envelope
Edward Geisinger•Nadav J. Mortman•Yunfei Dai•Murat Cokol•Sapna Syal等 13 人
Nature Communications
2020
•2020/9/9
•Vol.11 No.1 p.1-16
A unique, protective cell envelope contributes to the broad drug resistance of the nosocomial pathogen Acinetobacter baumannii. Here we use transposon insertion sequencing to identify A. baumannii mutants displaying altered susceptibility to a panel of diverse antibiotics. By examining mutants with ...
AntimicrobialsCellular microbiologyDNA replicationMicrobial genetics
10.1038/S41467-020-18301-2
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
Genetic fusions favor tumorigenesis through degron loss in oncogenes
Liu Jing•Tokheim Collin•Lee Jonathan D.•Gan Wenjian•North Brian J.等 8 人
Nature Communications
2021
•2021/11/18
•Vol.12 No.1 p.1-15
Chromosomal rearrangements can generate genetic fusions composed of two distinct gene sequences, many of which have been implicated in tumorigenesis and progression. Our study proposes a model whereby oncogenic gene fusions frequently alter the protein stability of the resulting fusion products, via...
Cancer geneticsCancer genomicsOncogenesUbiquitin ligasesUbiquitylation
10.1038/S41467-021-26871-Y
ISSN:2041-1723
The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state
Atwal Sharanjeet•Wongsantichon Jantana•Giengkam Suparat•Saharat Kittirat•Pittayasathornthun Yanin Jaiyen等 12 人
Nature Communications
2022
•2022/6/23
•Vol.13 No.1 p.1-12
Orientia tsutsugamushi (Ot) is an obligate intracellular bacterium in the family Rickettsiaceae that causes scrub typhus, a severe mite-borne human disease. Its mechanism of cell exit is unusual amongst Rickettsiaceae, as Ot buds off the surface of infected cells enveloped in plasma membrane. Here, ...
Bacterial developmentCellular microbiology
10.1038/S41467-022-31176-9
ISSN:2041-1723
Spatiotemporally resolved mapping of extracellular proteomes via in vivo-compatible TyroID
Zijuan Zhang•Yankun Wang•Wenjie Lu•Xiaofei Wang•Hongyang Guo等 9 人
Nature Communications
2025
•2025/3/15
•Vol.16 No.1 p.1-23
Extracellular proteins play pivotal roles in both intracellular signaling and intercellular communications in health and disease. While recent advancements in proximity labeling (PL) methods, such as peroxidase- and photocatalyst-based approaches, have facilitated the resolution of extracellular pro...
Chemical modificationProtein–protein interaction networksProteomic analysis
10.1038/S41467-025-57767-W
ISSN:2041-1723
Subgenome dominance shapes novel gene evolution in the decaploid pitcher plant Nepenthes gracilis
Franziska Saul•Mathias Scharmann•Takanori Wakatake•Sitaram Rajaraman•André Marques等 22 人
Nature Plants
2023
•2023/11/23
•00 p.1-16
Subgenome dominance after whole-genome duplication generates distinction in gene number and expression at the level of chromosome sets, but it remains unclear how this process may be involved in evolutionary novelty. Here we generated a chromosome-scale genome assembly of the Asian pitcher plant Nep...
GeneticsPlant sciences
10.1038/S41477-023-01562-2
ISSN:2055-0278
Deep learning reveals antibiotics in the archaeal proteome
Marcelo D. T. Torres•Fangping Wan•Cesar de la Fuente-Nunez
Nature Microbiology
2025
•2025/8/12
•00 p.1-15
Antimicrobial resistance is one of the greatest threats facing humanity, making the need for new antibiotics more critical than ever. While most antibiotics originate from bacteria and fungi, archaea offer a largely untapped reservoir for antibiotic discovery. In this study, we leveraged deep learni...
AntimicrobialsMicrobiology
10.1038/S41564-025-02061-0
ISSN:2058-5276
Sarcosine decreases in sarcopenia and enhances muscle regeneration and adipose thermogenesis by activating anti-inflammatory macrophages
Yu Liu•Meiling Ge•Xina Xiao•Ying Lu•Wanyu Zhao等 26 人
Nature Aging
2025
•2025/6/23
•00 p.1-18
Age-related changes in circulating metabolites influence systemic physiology and may contribute to diseases such as sarcopenia. Although metabolic dysregulation is closely linked to sarcopenia, the roles of specific metabolites remain unclear. In this study, we performed comprehensive plasma metabol...
AgeingMetabolomicsProteomics
10.1038/S43587-025-00900-7
ISSN:2662-8465
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
Dietary restriction transforms the mammalian protein persulfidome in a tissue-specific and cystathionine γ-lyase-dependent manner
Nazmin Bithi•Christopher Link•Yoko O. Henderson•Suzie Kim•Jie Yang等 9 人
Nature Communications
2021
•2021/3/19
•Vol.12 No.1 p.1-20
Hydrogen sulfide (H2S) is a cytoprotective redox-active metabolite that signals through protein persulfidation (R-SSnH). Despite the known importance of persulfidation, tissue-specific persulfidome profiles and their associated functions are not well characterized, specifically under conditions and ...
AgeingMetabolismPost-translational modificationsProteomics
10.1038/S41467-021-22001-W
ISSN:2041-1723
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
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
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
Three chromosome-level duck genome assemblies provide insights into genomic variation during domestication
Zhu Feng•Yin Zhong-Tao•Wang Zheng•Smith Jacqueline•Zhang Fan等 22 人
Nature Communications
2021
•2021/10/11
•Vol.12 No.1 p.1-11
Domestic ducks are raised for meat, eggs and feather down, and almost all varieties are descended from the Mallard (Anas platyrhynchos). Here, we report chromosome-level high-quality genome assemblies for meat and laying duck breeds, and the Mallard. Our new genomic databases contain annotations for...
Agricultural geneticsGenomics
10.1038/S41467-021-26272-1
ISSN:2041-1723
Decoding chromatin states by proteomic profiling of nucleosome readers
Saulius Lukauskas•Andrey Tvardovskiy•Nhuong V. Nguyen•Mara Stadler•Peter Faull等 20 人
Nature
2024
•2024/3/6
•00 p.1-9
DNA and histone modifications combine into characteristic patterns that demarcate functional regions of the genome1,2. While many ‘readers’ of individual modifications have been described3–5, how chromatin states comprising composite modification signatures, histone variants and internucleosomal lin...
EpigeneticsHistone post-translational modificationsProtein databasesProtein–protein interaction networksProteome informatics
10.1038/S41586-024-07141-5
ISSN:0028-0836
Programming multicellular assembly with synthetic cell adhesion molecules
Stevens Adam J.•Harris Andrew R.•Gerdts Josiah•Kim Ki H.•Trentesaux Coralie等 11 人
Nature
2022
•2022/12/12
•Vol.614 No.7946 p.144-152
Cell adhesion molecules are ubiquitous in multicellular organisms, specifying precise cell–cell interactions in processes as diverse as tissue development, immune cell trafficking and the wiring of the nervous system1–4. Here we show that a wide array of synthetic cell adhesion molecules can be gene...
CadherinsIntegrinsProtein engineeringSynthetic biologyTissue engineering
10.1038/S41586-022-05622-Z
ISSN:0028-0836
A secreted endosymbiont protein essential for colonizing host cells
Gerald P. Maeda•Allen Z. Xue•Ethan W. Yu•Aadhunik Sundar•Derrick L. Kamp等 8 人
Nature
2026
•2026/7/1
•00 p.1-9
Intracellular bacterial symbioses have arisen myriad times in eukaryotes, with dozens known from insects alone1,2. Beginning with Buchnera, the obligate endosymbiont of aphids, genomes of endosymbionts have illuminated their evolutionary origins and metabolic contributions to hosts3,4. However, the ...
Bacterial genesCoevolutionSymbiosis
10.1038/S41586-026-10711-4
ISSN:0028-0836
Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages
Ng Charlotte K. Y.•Dazert Eva•Boldanova Tuyana•Coto-Llerena Mairene•Nuciforo Sandro等 19 人
Nature Communications
2022
•2022/5/4
•Vol.13 No.1 p.1-18
Proteogenomic analyses of hepatocellular carcinomas (HCC) have focused on early-stage, HBV-associated HCCs. Here we present an integrated proteogenomic analysis of HCCs across clinical stages and etiologies. Pathways related to cell cycle, transcriptional and translational control, signaling transdu...
Cancer genomicsHepatocellular carcinomaPhosphoproteinsProteomicsTumour heterogeneity
10.1038/S41467-022-29960-8
ISSN:2041-1723
An extended reconstruction of human gut microbiota metabolism of dietary compounds
Blasco Telmo•Pérez-Burillo Sergio•Balzerani Francesco•Hinojosa-Nogueira Daniel•Lerma-Aguilera Alberto等 14 人
Nature Communications
2021
•2021/8/5
•Vol.12 No.1 p.1-12
Understanding how diet and gut microbiota interact in the context of human health is a key question in personalized nutrition. Genome-scale metabolic networks and constraint-based modeling approaches are promising to systematically address this complex problem. However, when applied to nutritional q...
Biochemical reaction networksComputational models
10.1038/S41467-021-25056-X
ISSN:2041-1723
Regulation of micro- and small-exon retention and other splicing processes by GRP20 for flower development
Jun Wang•Xinwei Ma•Yi Hu•Guanhua Feng•Chunce Guo等 7 人
Nature Plants
2024
•2024/1/9
•00 p.1-20
Pre-mRNA splicing is crucial for gene expression and depends on the spliceosome and splicing factors. Plant exons have an average size of ~180 nucleotides and typically contain motifs for interactions with spliceosome and splicing factors. Micro exons (<51 nucleotides) are found widely in eukaryo...
Plant developmentPlant molecular biology
10.1038/S41477-023-01605-8
ISSN:2055-0278
An orthogonal metabolic framework for one-carbon utilization
Chou Alexander•Lee Seung Hwan•Zhu Fayin•Clomburg James M.•Gonzalez Ramon
Nature Metabolism
2021
•2021/10/21
•Vol.3 No.10 p.1385-1399
Metabolic engineering often entails concurrent engineering of substrate utilization, central metabolism and product synthesis pathways, inevitably creating interdependency with native metabolism. Here we report an alternative approach using synthetic pathways for C1 bioconversion that generate multi...
Metabolic engineeringMetabolism
10.1038/S42255-021-00453-0
ISSN:2522-5812