Nature Structural &Molecular Biology最新文献

Author Correction: Structural basis of tRNA recognition by the m³C RNA methyltransferase METTL6 in complex with SerRS seryl-tRNA synthetase. 作者更正：m3C RNA 甲基转移酶 METTL6 与 SerRS 丝氨酰-tRNA 合成酶复合体识别 tRNA 的结构基础。

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2025-02-04 DOI: 10.1038/s41594-025-01508-6

Philipp Throll, Luciano G Dolce, Palma Rico-Lastres, Katharina Arnold, Laura Tengo, Shibom Basu, Stefanie Kaiser, Robert Schneider, Eva Kowalinski

引用次数: 0

Closed and open structures of the eukaryotic magnesium channel Mrs2 reveal the auto-ligand-gating regulation mechanism. 真核镁通道Mrs2的封闭和开放结构揭示了自配体门控调控机制。

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2024-11-28 DOI: 10.1038/s41594-024-01432-1

Ping Li, Shiyan Liu, Johan Wallerstein, Rhiza Lyne E Villones, Peng Huang, Karin Lindkvist-Petersson, Gabriele Meloni, Kefeng Lu, Kristine Steen Jensen, Sara I Liin, Pontus Gourdon

{"title":"Closed and open structures of the eukaryotic magnesium channel Mrs2 reveal the auto-ligand-gating regulation mechanism.","authors":"Ping Li, Shiyan Liu, Johan Wallerstein, Rhiza Lyne E Villones, Peng Huang, Karin Lindkvist-Petersson, Gabriele Meloni, Kefeng Lu, Kristine Steen Jensen, Sara I Liin, Pontus Gourdon","doi":"10.1038/s41594-024-01432-1","DOIUrl":"10.1038/s41594-024-01432-1","url":null,"abstract":"The CorA/Mrs2 family of pentameric proteins are cardinal for the influx of Mg2+ across cellular membranes, importing the cation to mitochondria in eukaryotes. Yet, the conducting and regulation mechanisms of permeation remain elusive, particularly for the eukaryotic Mrs2 members. Here, we report closed and open Mrs2 cryo-electron microscopy structures, accompanied by functional characterization. Mg2+ flux is permitted by a narrow pore, gated by methionine and arginine residues in the closed state. Transition between the conformations is orchestrated by two pairs of conserved sensor-serving Mg2+-binding sites in the mitochondrial matrix lumen, located in between monomers. At lower levels of Mg2+, these ions are stripped, permitting an alternative, symmetrical shape, maintained by the RDLR motif that replaces one of the sensor site pairs in the open conformation. Thus, our findings collectively establish the molecular basis for selective Mg2+ influx of Mrs2 and an auto-ligand-gating regulation mechanism.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":" ","pages":""},"PeriodicalIF":16.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751154","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

Structure and function of the human mitochondrial MRS2 channel. 人线粒体MRS2通道的结构和功能。

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2024-11-28 DOI: 10.1038/s41594-024-01420-5

Zhihui He, Yung-Chi Tu, Chen-Wei Tsai, Jonathan Mount, Jingying Zhang, Ming-Feng Tsai, Peng Yuan

{"title":"Structure and function of the human mitochondrial MRS2 channel.","authors":"Zhihui He, Yung-Chi Tu, Chen-Wei Tsai, Jonathan Mount, Jingying Zhang, Ming-Feng Tsai, Peng Yuan","doi":"10.1038/s41594-024-01420-5","DOIUrl":"10.1038/s41594-024-01420-5","url":null,"abstract":"The human mitochondrial RNA splicing 2 protein (MRS2) has been implicated in Mg2+ transport across mitochondrial inner membranes, thus having an important role in Mg2+ homeostasis critical for mitochondrial integrity and function. However, the molecular mechanisms underlying its fundamental channel properties such as ion selectivity and regulation remain unclear. Here we present a structural and functional investigation of MRS2. Cryo-electron microscopy structures in various ionic conditions reveal a pentameric channel architecture and the molecular basis of ion permeation and potential regulation mechanisms. Electrophysiological analyses demonstrate that MRS2 is a Ca2+-regulated, nonselective channel permeable to Mg2+, Ca2+, Na+ and K+, which contrasts with its prokaryotic ortholog, CorA, operating as a Mg2+-gated Mg2+ channel. Moreover, a conserved arginine ring within the pore of MRS2 functions to restrict cation movements, thus preventing the channel from collapsing the proton motive force that drives mitochondrial adenosine triphosphate synthesis. Together, our results provide a molecular framework for further understanding MRS2 in mitochondrial function and disease.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":" ","pages":""},"PeriodicalIF":16.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751090","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

Structural basis of nucleosome transcription mediated by Chd1 and FACT Chd1和FACT介导核小体转录的结构基础

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2020-11-30 DOI: 10.1101/2020.11.30.403857

L. Farnung, M. Ochmann, M. Engeholm, P. Cramer

{"title":"Structural basis of nucleosome transcription mediated by Chd1 and FACT","authors":"L. Farnung, M. Ochmann, M. Engeholm, P. Cramer","doi":"10.1101/2020.11.30.403857","DOIUrl":"https://doi.org/10.1101/2020.11.30.403857","url":null,"abstract":"Efficient transcription of RNA polymerase II (Pol II) through nucleosomes requires the help of various factors. Here we show biochemically that Pol II transcription through a nucleosome is facilitated by the chromatin remodeler Chd1 and the histone chaperone FACT when the elongation factors Spt4/5 and TFIIS are present. We report cryo-EM structures of transcribing Saccharomyces cerevisiae Pol II−Spt4/5−nucleosome complexes with bound Chd1 or FACT. In the first structure, Pol II transcription exposes the proximal histone H2A−H2B dimer that is bound by Spt5. Pol II has also released the inhibitory DNA-binding region of Chd1 that is poised to pump DNA toward Pol II. In the second structure, Pol II has generated a partially unraveled nucleosome that binds FACT, which excludes Chd1 and Spt5. These results suggest that Pol II progression through a nucleosome activates Chd1, enables FACT binding and eventually triggers transfer of FACT together with histones to upstream DNA. Structural and functional analyses of RNA polymerase II−nucleosome complexes reveal how the chromatin remodeler Chd1 and the histone chaperone FACT mediate Pol II transcription through a nucleosome.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"28 1","pages":"382 - 387"},"PeriodicalIF":16.8,"publicationDate":"2020-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42190486","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: 55

Cryo-EM structures of human RNA polymerase III in its unbound and transcribing states 人RNA聚合酶III非结合状态和转录状态的低温电镜结构

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2020-06-29 DOI: 10.1101/2020.06.29.177642

M. Girbig, A. Misiaszek, Matthias K. Vorländer, Aleix Lafita, H. Grötsch, F. Baudin, A. Bateman, C. Müller

{"title":"Cryo-EM structures of human RNA polymerase III in its unbound and transcribing states","authors":"M. Girbig, A. Misiaszek, Matthias K. Vorländer, Aleix Lafita, H. Grötsch, F. Baudin, A. Bateman, C. Müller","doi":"10.1101/2020.06.29.177642","DOIUrl":"https://doi.org/10.1101/2020.06.29.177642","url":null,"abstract":"RNA polymerase III (Pol III) synthesizes transfer RNAs and other short, essential RNAs. Human Pol III misregulation is linked to tumor transformation, neurodegenerative and developmental disorders, and increased sensitivity to viral infections. Here, we present cryo-electron microscopy structures at 2.8 to 3.3 Å resolution of transcribing and unbound human Pol III. We observe insertion of the TFIIS-like subunit RPC10 into the polymerase funnel, providing insights into how RPC10 triggers transcription termination. Our structures resolve elements absent from Saccharomyces cerevisiae Pol III such as the winged-helix domains of RPC5 and an iron–sulfur cluster, which tethers the heterotrimer subcomplex to the core. The cancer-associated RPC7α isoform binds the polymerase clamp, potentially interfering with Pol III inhibition by tumor suppressor MAF1, which may explain why overexpressed RPC7α enhances tumor transformation. Finally, the human Pol III structure allows mapping of disease-related mutations and may contribute to the development of inhibitors that selectively target Pol III for therapeutic interventions. Cryo-EM structures of human Pol III in both apo- and elongating states reveal metazoan-specific differences in the regulation of transcription termination and identify mutations relevant to human disease.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"28 1","pages":"210 - 219"},"PeriodicalIF":16.8,"publicationDate":"2020-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42310095","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: 40

Structural and functional characterization of the Spo11 core complex Spo11核配合物的结构与功能表征

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2020-02-24 DOI: 10.1101/2020.02.21.960211

Corentin Claeys Bouuaert, Sam E. Tischfield, Stephen Pu, Eleni P. Mimitou, E. Arias-Palomo, J. Berger, S. Keeney

{"title":"Structural and functional characterization of the Spo11 core complex","authors":"Corentin Claeys Bouuaert, Sam E. Tischfield, Stephen Pu, Eleni P. Mimitou, E. Arias-Palomo, J. Berger, S. Keeney","doi":"10.1101/2020.02.21.960211","DOIUrl":"https://doi.org/10.1101/2020.02.21.960211","url":null,"abstract":"Spo11, which makes DNA double-strand breaks (DSBs) that are essential for meiotic recombination, has long been recalcitrant to biochemical study. We provide molecular analysis of Saccharomyces cerevisiae Spo11 purified with partners Rec102, Rec104 and Ski8. Rec102 and Rec104 jointly resemble the B subunit of archaeal topoisomerase VI, with Rec104 occupying a position similar to the Top6B GHKL-type ATPase domain. Unexpectedly, the Spo11 complex is monomeric (1:1:1:1 stoichiometry), consistent with dimerization controlling DSB formation. Reconstitution of DNA binding reveals topoisomerase-like preferences for duplex–duplex junctions and bent DNA. Spo11 also binds noncovalently but with high affinity to DNA ends mimicking cleavage products, suggesting a mechanism to cap DSB ends. Mutations that reduce DNA binding in vitro attenuate DSB formation, alter DSB processing and reshape the DSB landscape in vivo. Our data reveal structural and functional similarities between the Spo11 core complex and Topo VI, but also highlight differences reflecting their distinct biological roles. Biochemical and structural characterization of the meiotic DSB core complex of budding yeast reveals molecular architecture and DNA-binding properties similar to those of ancestral Topo VI.","PeriodicalId":18836,"journal":{"name":"Nature Structural &Molecular Biology","volume":"28 1","pages":"92 - 102"},"PeriodicalIF":16.8,"publicationDate":"2020-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49195616","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: 27

Engaging the public 让公众参与

IF 16.8 1区生物学

Nature Structural &Molecular Biology Pub Date : 2020-01-16 DOI: 10.1201/9781315384467-5

Emily Troshynski

引用次数: 27