Nature Structural &Molecular Biology最新文献

Author Correction: Recruitment of Atg1 to the phagophore by Atg8 orchestrates autophagy machineries. 作者更正：Atg8将Atg1招募到吞噬体中协调自噬机制。

IF 10.1 1区生物学

Nature Structural &Molecular Biology Pub Date : 2025-10-13 DOI: 10.1038/s41594-025-01700-8

Jing-Zhen Song, Hui Li, Haiyan Yang, Rui Liu, Wenting Zhang, Tianlong He, Meng-Xi Xie, Chen Chen, Li Cui, Shian Wu, Yueguang Rong, Li-Feng Pan, Jing Zhu, Qingqiu Gong, Juan Wang, Zhao Qin, Zhiping Xie

引用次数: 0

Structural phylogenetics unravels the evolutionary diversification of communication systems in gram-positive bacteria and their viruses. 结构系统发育揭示了革兰氏阳性细菌及其病毒通信系统的进化多样化。

IF 10.1 1区生物学

Nature Structural &Molecular Biology Pub Date : 2025-10-10 DOI: 10.1038/s41594-025-01649-8

David Moi, Charles Bernard, Martin Steinegger, Yannis Nevers, Mauricio Langleib, Christophe Dessimoz

{"title":"Structural phylogenetics unravels the evolutionary diversification of communication systems in gram-positive bacteria and their viruses.","authors":"David Moi, Charles Bernard, Martin Steinegger, Yannis Nevers, Mauricio Langleib, Christophe Dessimoz","doi":"10.1038/s41594-025-01649-8","DOIUrl":"https://doi.org/10.1038/s41594-025-01649-8","url":null,"abstract":"Recent advances in artificial-intelligence-based protein structure modeling have yielded remarkable progress in predicting protein structures. Because structures are constrained by their biological function, their geometry tends to evolve more slowly than the underlying amino acids sequences. This feature of structures could in principle be used to reconstruct phylogenetic trees over longer evolutionary timescales than sequence-based approaches; however, until now, a reliable structure-based tree-building method has been elusive. Here, we introduce a rigorous framework for empirical tree accuracy evaluation and tested multiple approaches using sequence and structure information. The best results were obtained by inferring trees from sequences aligned using a local structural alphabet-an approach robust to conformational changes that confound traditional structural distance measures. We illustrate the power of structure-informed phylogenetics by deciphering the evolutionary diversification of a particularly challenging family: the fast-evolving RRNPPA quorum-sensing receptors. We were able to propose a more parsimonious evolutionary history for this critical protein family that enables gram-positive bacteria, plasmids and bacteriophages to communicate and coordinate key behaviors. The advent of high-accuracy structural phylogenetics enables a myriad of applications across biology, such as uncovering deeper evolutionary relationships, elucidating unknown protein functions or refining the design of bioengineered molecules.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The human ribosome modulates multidomain protein biogenesis by delaying cotranslational domain docking. 人类核糖体通过延迟共翻译结构域对接来调节多结构域蛋白的生物发生。

IF 10.1 1区生物学

Nature Structural &Molecular Biology Pub Date : 2025-09-19 DOI: 10.1038/s41594-025-01676-5

Grant A Pellowe, Tomas B Voisin, Laura Karpauskaite, Sarah L Maslen, Alžběta Roeselová, J Mark Skehel, Chloe Roustan, Roger George, Andrea Nans, Svend Kjær, Ian A Taylor, David Balchin

{"title":"The human ribosome modulates multidomain protein biogenesis by delaying cotranslational domain docking.","authors":"Grant A Pellowe, Tomas B Voisin, Laura Karpauskaite, Sarah L Maslen, Alžběta Roeselová, J Mark Skehel, Chloe Roustan, Roger George, Andrea Nans, Svend Kjær, Ian A Taylor, David Balchin","doi":"10.1038/s41594-025-01676-5","DOIUrl":"https://doi.org/10.1038/s41594-025-01676-5","url":null,"abstract":"Proteins with multiple domains are intrinsically prone to misfold, yet fold efficiently during their synthesis on the ribosome. This is especially important in eukaryotes, where multidomain proteins predominate. Here we sought to understand how multidomain protein folding is modulated by the eukaryotic ribosome. We used hydrogen-deuterium exchange mass spectrometry and cryo-electron microscopy to characterize the structure and dynamics of partially synthesized intermediates of a model multidomain protein. We find that nascent subdomains fold progressively during synthesis on the human ribosome, templated by interactions across domain interfaces. The conformational ensemble of the nascent chain is tuned by its unstructured C-terminal segments, which keep interfaces between folded domains in dynamic equilibrium until translation termination. This contrasts with the bacterial ribosome, on which domain interfaces form early and remain stable during synthesis. Delayed domain docking may avoid interdomain misfolding to promote the maturation of multidomain proteins in eukaryotes.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Addendum: Retinoic acid signaling is critical during the totipotency window in early mammalian development. 附录：维甲酸信号在哺乳动物早期发育的全能性窗口期是至关重要的。

IF 10.1 1区生物学

Nature Structural &Molecular Biology Pub Date : 2025-09-02 DOI: 10.1038/s41594-025-01661-y

Ane Iturbide, Mayra L Ruiz Tejada Segura, Camille Noll, Kenji Schorpp, Ina Rothenaigner, Elias R Ruiz-Morales, Gabriele Lubatti, Ahmed Agami, Kamyar Hadian, Antonio Scialdone, Maria-Elena Torres-Padilla

引用次数: 0

Nucleosomes constrain 1D DNA diffusion by eukaryotic transcription factors. 核小体通过真核转录因子约束1D DNA扩散。

IF 10.1 1区生物学

Nature Structural &Molecular Biology Pub Date : 2025-08-19 DOI: 10.1038/s41594-025-01658-7

引用次数: 0

Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug. 原生疟疾翻译机制的综合结构生物学及其抗疟疾药物的抑制作用。

IF 10.1 1区生物学

Nature Structural &Molecular Biology Pub Date : 2025-08-18 DOI: 10.1038/s41594-025-01632-3

Leonie Anton, Wenjing Cheng, Meseret T Haile, Jerzy M Dziekan, David W Cobb, Xiyan Zhu, Leyan Han, Emerson Li, Anjali Nair, Carolyn L Lee, Hanyu Wang, Hangjun Ke, Guoan Zhang, Emma H Doud, Alan F Cowman, Chi-Min Ho

{"title":"Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug.","authors":"Leonie Anton, Wenjing Cheng, Meseret T Haile, Jerzy M Dziekan, David W Cobb, Xiyan Zhu, Leyan Han, Emerson Li, Anjali Nair, Carolyn L Lee, Hanyu Wang, Hangjun Ke, Guoan Zhang, Emma H Doud, Alan F Cowman, Chi-Min Ho","doi":"10.1038/s41594-025-01632-3","DOIUrl":"10.1038/s41594-025-01632-3","url":null,"abstract":"Our understanding of cellular events is hampered by the gap between the resolution at which we can observe events inside cells and our ability to replicate physiological conditions in test tubes. Here, we show in Plasmodium falciparum, a non-model organism of high medical importance, that this gap can be bridged by using an integrated structural biology approach to visualize events inside the cell at molecular resolution. We determined eight high-resolution structures of the native malarial ribosome in actively translating states inside P. falciparum-infected human erythrocytes using in situ cryo-electron tomography. Following perturbation with a Plasmodium-specific translation inhibitor, we then observed a decrease in elongation factor-bound ribosomal states and an apparent upregulation of ribosome biogenesis in inhibitor-treated parasites. Our work elucidates new molecular details of the malarial translation elongation cycle and demonstrates direct multiscale visualization of drug-induced phenotypic changes in the structure and localization of individual molecules within the native cellular context.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-cell long-read Hi-C, scNanoHi-C2, details 3D genome reorganization in embryonic-stage germ cells. 单细胞长读Hi-C， scNanoHi-C2，详细描述胚胎期生殖细胞的三维基因组重组。

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2025-07-04 DOI: 10.1038/s41594-025-01604-7

Jiansen Lu, Wen Li, Fuchou Tang

{"title":"Single-cell long-read Hi-C, scNanoHi-C2, details 3D genome reorganization in embryonic-stage germ cells.","authors":"Jiansen Lu, Wen Li, Fuchou Tang","doi":"10.1038/s41594-025-01604-7","DOIUrl":"https://doi.org/10.1038/s41594-025-01604-7","url":null,"abstract":"During mouse development, embryonic-stage germ cells (EGCs) make crucial fate decisions, with female EGCs embarking on meiosis whereas male EGCs enter mitotic arrest until birth. Despite increasing understanding of the reprogramming of epigenetic modifications, the dynamics of three-dimensional (3D) genome structures within individual EGCs remains elusive. Here we present a single-cell input, long-read Hi-C method, termed scNanoHi-C2. We use scNanoHi-C2 to systematically dissect the dynamics of EGC chromatin structures. We find that, despite changes in autosomes similar to spermatogenesis, the X chromosomes of female EGCs show enhanced specific interactions between B compartments. By reconstructing 3D genome models, we observe dynamic chromosome positioning during meiosis, showing that the neighborhood between nonhomologous chromosomes of EGCs is relatively random. Simultaneously, transposable elements undergo dramatic chromatin reorganization and display an asymmetric distribution of Alu/B2 elements around meiotic topologically associated domain boundaries. Moreover, we find that high-order interactions in EGCs at the mitosis stage are mainly enriched in the B compartment, whereas, after the mitosis-to-meiosis transition, enriched high-order interactions shift to refined A compartments, to potentially promote meiotic-specific transcription programs during global genomic condensation. We also reveal an unexpected chromatin structure in mitotic-arrested male EGCs distinct from the previously assumed G0 status, which may prime the unique genome structure for subsequent spermatogenesis. Altogether, our study highlights the potential of scNanoHi-C2 and reveals key features of the chromatin structure reprogramming in EGCs.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":" ","pages":""},"PeriodicalIF":16.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural basis for Parkinson’s disease-linked LRRK2’s binding to microtubules 帕金森病相关LRRK2与微管结合的结构基础

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2022-01-22 DOI: 10.1101/2022.01.21.477284

D. Snead, M. Matyszewski, Andrea M. Dickey, Yu Lin, A. Leschziner, Samara L. Reck-Peterson

引用次数: 11

Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics 恶唑烷酮类抗生素对翻译特异性抑制的结构基础

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2021-08-10 DOI: 10.1101/2021.08.10.455846

K. Tsai, Vanja Stojković, D. J. Lee, Iris D. Young, Teresa Szal, N. Vázquez-Laslop, A. Mankin, James S. Fraser, D. Fujimori

{"title":"Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics","authors":"K. Tsai, Vanja Stojković, D. J. Lee, Iris D. Young, Teresa Szal, N. Vázquez-Laslop, A. Mankin, James S. Fraser, D. Fujimori","doi":"10.1101/2021.08.10.455846","DOIUrl":"https://doi.org/10.1101/2021.08.10.455846","url":null,"abstract":"The antibiotic linezolid, the first clinically approved member of the oxazolidinone class, inhibits translation of bacterial ribosomes by binding to the peptidyl transferase center. Recent work has demonstrated that linezolid does not inhibit peptide bond formation at all sequences but rather acts in a context-specific manner, namely when alanine occupies the penultimate position of the nascent chain. In this study, we determined that the second-generation oxazolidinone radezolid also induces stalling with alanine at the penultimate position. However, the molecular basis for context-specificity of these inhibitors has not been elucidated. In this study, we determined high-resolution cryo-EM structures of both linezolid and radezolid-stalled ribosome complexes. These structures reveal that the alanine side chain fits within a small hydrophobic crevice created by oxazolidinone, resulting in improved ribosome binding. Modification of the ribosome by the antibiotic resistance enzyme Cfr disrupts stalling by forcing the antibiotic to adopt a conformation that narrows the hydrophobic alanine pocket. Together, the structural and biochemical findings presented in this work provide molecular understanding of context-specific inhibition of translation by clinically important oxazolidinone antibiotics.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"1 1","pages":""},"PeriodicalIF":16.8,"publicationDate":"2021-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"62332424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Higher-order phosphatase–substrate contacts terminate the integrated stress response 高阶磷酸酶-底物接触终止了综合应力响应

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2021-06-18 DOI: 10.1101/2021.06.18.449003

Yahui Yan, H. Harding, D. Ron

{"title":"Higher-order phosphatase–substrate contacts terminate the integrated stress response","authors":"Yahui Yan, H. Harding, D. Ron","doi":"10.1101/2021.06.18.449003","DOIUrl":"https://doi.org/10.1101/2021.06.18.449003","url":null,"abstract":"Many regulatory PPP1R subunits join few catalytic PP1c subunits to mediate phosphoserine and phosphothreonine dephosphorylation in metazoans. Regulatory subunits engage the surface of PP1c, locally affecting flexible access of the phosphopeptide to the active site. However, catalytic efficiency of holophosphatases towards their phosphoprotein substrates remains unexplained. Here we present a cryo-EM structure of the tripartite PP1c–PPP1R15A–G-actin holophosphatase that terminates signaling in the mammalian integrated stress response (ISR) in the pre-dephosphorylation complex with its substrate, translation initiation factor 2α (eIF2α). G-actin, whose essential role in eIF2α dephosphorylation is supported crystallographically, biochemically and genetically, aligns the catalytic and regulatory subunits, creating a composite surface that engages the N-terminal domain of eIF2α to position the distant phosphoserine-51 at the active site. Substrate residues that mediate affinity for the holophosphatase also make critical contacts with eIF2α kinases. Thus, a convergent process of higher-order substrate recognition specifies functionally antagonistic phosphorylation and dephosphorylation in the ISR. Structures of the dephosphorylation complex for phosphorylated eIF2α reveal how contacts with the regulatory PPP1R15A subunit mediate substrate selectivity, providing a paradigm for dephosphorylation reactions by diverse combinatorially assembled holophosphatases.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"28 1","pages":"835 - 846"},"PeriodicalIF":16.8,"publicationDate":"2021-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49110087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6