Nature structural & molecular biology最新文献_第3页

Author Correction: Structural basis of the histone ubiquitination read-write mechanism of RYBP-PRC1. 作者更正：RYBP-PRC1组蛋白泛素化读写机制的结构基础。

Nature structural & molecular biology Pub Date : 2025-08-27 DOI: 10.1038/s41594-025-01674-7

Maria Ciapponi,Elena Karlukova,Sven Schkölziger,Christian Benda,Jürg Müller

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Structural basis for lipid transport at membrane contact sites by the IST2–OSH6 complex IST2-OSH6复合物在膜接触部位脂质运输的结构基础

Nature structural & molecular biology Pub Date : 2025-08-27 DOI: 10.1038/s41594-025-01660-z

Melanie Arndt, Angela Schweri, Raimund Dutzler

{"title":"Structural basis for lipid transport at membrane contact sites by the IST2–OSH6 complex","authors":"Melanie Arndt, Angela Schweri, Raimund Dutzler","doi":"10.1038/s41594-025-01660-z","DOIUrl":"https://doi.org/10.1038/s41594-025-01660-z","url":null,"abstract":"Membrane contact sites are hubs for interorganellar lipid transport within eukaryotic cells. As a principal tether bridging the endoplasmic reticulum (ER) and the plasma membrane in Saccharomyces cerevisiae, the protein IST2 has a major role during lipid transport between both compartments. Here, we show a comprehensive investigation elucidating the structural and mechanistic properties of IST2 and its interaction with the soluble lipid transfer protein OSH6. The ER-embedded transmembrane domain of IST2 is homologous to the TMEM16 family and acts as a constitutively active lipid scramblase. The extended C terminus binds to the plasma membrane and the phosphatidylserine–phosphatidylinositol 4-phosphate exchanger OSH6. Through cellular growth assays and biochemical and structural studies, we characterized the interaction between both proteins and show that OSH6 remains associated with IST2 during lipid shuttling between membranes. These results highlight the role of the IST2–OSH6 complex in lipid trafficking and offer initial insights into the relevance of scramblases for carrier-like lipid transport mechanisms.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"116 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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The mitotic STAG3–cohesin complex shapes male germline nucleome 有丝分裂的stag3 -内聚复合体形成雄性种系核体

Nature structural & molecular biology Pub Date : 2025-08-25 DOI: 10.1038/s41594-025-01647-w

Masahiro Nagano, Bo Hu, Kosuke Ogata, Fumiya Umemura, Yukiko Ishikura, Shinnosuke Suzuki, Christos C. Katsifis, Masanori Yoshinaga, Gabriele Litos, Kota Nagasaka, Wen Tang, Yoshiaki Nosaka, Hiromichi Sasada, Hanbo Wang, Daichi Kondo, Yoshitaka Katou, Ken Mizuta, Yukihiro Yabuta, Hiroshi Ohta, Francisca Nathalia de Luna Vitorino, Hiroshi Arima, Takafumi Ichikawa, Michele Gabriele, Jacek Majewski, Benjamin A. Garcia, Osamu Takeuchi, Shosei Yoshida, Anders S. Hansen, Jan-Michael Peters, Yasushi Ishihama, Mitinori Saitou

{"title":"The mitotic STAG3–cohesin complex shapes male germline nucleome","authors":"Masahiro Nagano, Bo Hu, Kosuke Ogata, Fumiya Umemura, Yukiko Ishikura, Shinnosuke Suzuki, Christos C. Katsifis, Masanori Yoshinaga, Gabriele Litos, Kota Nagasaka, Wen Tang, Yoshiaki Nosaka, Hiromichi Sasada, Hanbo Wang, Daichi Kondo, Yoshitaka Katou, Ken Mizuta, Yukihiro Yabuta, Hiroshi Ohta, Francisca Nathalia de Luna Vitorino, Hiroshi Arima, Takafumi Ichikawa, Michele Gabriele, Jacek Majewski, Benjamin A. Garcia, Osamu Takeuchi, Shosei Yoshida, Anders S. Hansen, Jan-Michael Peters, Yasushi Ishihama, Mitinori Saitou","doi":"10.1038/s41594-025-01647-w","DOIUrl":"https://doi.org/10.1038/s41594-025-01647-w","url":null,"abstract":"Germ cells are unique in that they tailor chromatin toward generating totipotency. Accordingly, mammalian spermatogonia, including spermatogonial stem cells that constitute the source for male gametes, acquire distinctive chromatin organization with weak insulation, but the underlying mechanism remains unknown. Here we show that STAG3, so far known to exclusively form meiotic cohesins, generates a mitotic cohesin for male germline nucleome programming in mice. Owing to its shorter chromatin residence, STAG3–cohesin attenuates topologically associating domains, rewires enhancer–promoter and Polycomb-mediated repressive interactions, and facilitates finer and more strengthened compartments, establishing a distinctive spermatogonial nucleome. Moreover, in the absence of STAG3–cohesin, spermatogonial stem cells show an impaired differentiation priming for spermatogenesis. Mitotic STAG3–cohesin is also expressed in human B cells and their malignant variations, promoting their propagation. Our findings on mitotic STAG3–cohesin elucidate a principle of male germline nucleome programming, demonstrate an unexpected mitotic role for STAG3 and might potentially improve understanding of human malignancies.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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A scaffold for quinone channeling between membrane and soluble bacterial oxidoreductases 醌在膜和可溶性细菌氧化还原酶之间通道的支架

Nature structural & molecular biology Pub Date : 2025-08-25 DOI: 10.1038/s41594-025-01607-4

M. Broc, M. V. Cherrier, A. Uzel, R. Arias-Cartin, P. Arnoux, G. Brasseur, F. Seduk, B. Guigliarelli, P. Legrand, F. Pierrel, G. Schoehn, M. J. Maté, L. Martin, S. Grimaldi, Y. Nicolet, A. Magalon, A. Walburger

{"title":"A scaffold for quinone channeling between membrane and soluble bacterial oxidoreductases","authors":"M. Broc, M. V. Cherrier, A. Uzel, R. Arias-Cartin, P. Arnoux, G. Brasseur, F. Seduk, B. Guigliarelli, P. Legrand, F. Pierrel, G. Schoehn, M. J. Maté, L. Martin, S. Grimaldi, Y. Nicolet, A. Magalon, A. Walburger","doi":"10.1038/s41594-025-01607-4","DOIUrl":"https://doi.org/10.1038/s41594-025-01607-4","url":null,"abstract":"Redox processes are at the heart of energetic metabolism that drives life on earth. By extension, complex and efficient electron transfer wires are necessary to connect the various metabolic pathways that are often located in distinct cellular compartments. Here, we uncovered a structural module that enables channeling of quinones from the membrane to various water-soluble redox catalytic units in prokaryotes. Using X-ray crystallography and cryo-electron microscopy, we determined the structure of the unusual bacterial formate dehydrogenase ForCE that contains four ForC catalytic subunits docked around a membrane-associated tetrameric ForE central scaffold. In the latter, a conserved domain that we propose to name helical membrane plugin (HMP) was identified as essential to link formate oxidation, in Bacillus subtilis, to the aerobic respiratory chain. Our bioinformatic analysis indicates that this HMP is associated with different quinone-reducing oxidoreductases, highlighting its broad importance as a functional unit to wire electrons between a given catalytic redox center and the quinone pool.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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DNA bendability regulates transcription factor binding to nucleosomes DNA可弯曲性调节转录因子与核小体的结合

Nature structural & molecular biology Pub Date : 2025-08-25 DOI: 10.1038/s41594-025-01633-2

Luca Mariani, Xiao Liu, Kwangwoon Lee, Stephen S. Gisselbrecht, Philip A. Cole, Martha L. Bulyk

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A structural window into the evolution of secondary transport mechanisms 次生输运机制演化的结构窗口

Nature structural & molecular biology Pub Date : 2025-08-25 DOI: 10.1038/s41594-025-01625-2

Samuel P. Berry, Rachelle Gaudet

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Evolutionary analysis reveals the origin of sodium coupling in glutamate transporters 进化分析揭示了谷氨酸转运体中钠偶联的起源

Nature structural & molecular biology Pub Date : 2025-08-25 DOI: 10.1038/s41594-025-01652-z

Krishna D. Reddy, Burha Rasool, Farideh Badichi Akher, Nemanja Kutlešić, Swati Pant, Olga Boudker

{"title":"Evolutionary analysis reveals the origin of sodium coupling in glutamate transporters","authors":"Krishna D. Reddy, Burha Rasool, Farideh Badichi Akher, Nemanja Kutlešić, Swati Pant, Olga Boudker","doi":"10.1038/s41594-025-01652-z","DOIUrl":"https://doi.org/10.1038/s41594-025-01652-z","url":null,"abstract":"Secondary active membrane transporters harness the energy of ion gradients to concentrate their substrates. Homologous transporters evolved to couple transport to different ions in response to changing environments and needs. The bases of such diversification and, thus, principles of ion coupling are unexplored. Here, using phylogenetics and ancestral protein reconstruction, we investigated sodium-coupled transport in prokaryotic glutamate transporters, a mechanism ubiquitous across life domains and critical to neurotransmitter recycling in humans by excitatory amino acid transporters from the solute carrier 1 family. By inferring ancestral prokaryotic transporter sequences during a change in the ion-coupling mechanism, we found an evolutionary transition from sodium-dependent to independent substrate binding and transport. Structural and functional experiments on ancestral transporters suggest that the transition involved allosteric mutations, rendering sodium binding dispensable without affecting the ion-binding sites. Allosteric tuning of transporters’ energy landscapes might be a widespread route of their functional diversification.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"29 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Activation of kainate receptor GluK2–Neto2 complex kainate受体GluK2-Neto2复合物的激活

Nature structural & molecular biology Pub Date : 2025-08-22 DOI: 10.1038/s41594-025-01656-9

Shanti Pal Gangwar, Maria V. Yelshanskaya, Laura Y. Yen, Thomas P. Newton, Alexander I. Sobolevsky

{"title":"Activation of kainate receptor GluK2–Neto2 complex","authors":"Shanti Pal Gangwar, Maria V. Yelshanskaya, Laura Y. Yen, Thomas P. Newton, Alexander I. Sobolevsky","doi":"10.1038/s41594-025-01656-9","DOIUrl":"https://doi.org/10.1038/s41594-025-01656-9","url":null,"abstract":"Kainate receptors (KARs) are tetrameric, ligand-gated ion channels of the ionotropic glutamate receptor family that mediate excitatory neurotransmission and modulate neuronal circuits and synaptic plasticity during development of the central nervous system. KARs are implicated in psychiatric and neurological diseases and represent a target of therapeutic intervention. Native KARs form complexes with neuropilin and tolloid-like auxiliary subunits (Neto1 and Neto2), which modulate their function, trafficking and synaptic localization. Here we present structures of rat GluK2 KAR in the apo closed state and in the open states activated by agonist kainate and positive allosteric modulator BPAM344, solved in the presence and absence of Neto2 using time-resolved cryo-electron microscopy. While the binding of Neto2 does not change the behavior of individual or dimeric ligand-binding domains (LBDs) or the ion channel, it prevents tightening of the interface between two LBD dimers during activation and slows the kinetics of deactivation. Our structures illuminate the mechanism of KAR activation and its modulation by Neto2.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Mechanisms and genomic implications of break-induced replication 断裂诱导复制的机制和基因组意义

Nature structural & molecular biology Pub Date : 2025-08-22 DOI: 10.1038/s41594-025-01644-z

Adel Atari, Haoyang Jiang, Roger A. Greenberg

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Midkine attenuates amyloid-β fibril assembly and plaque formation Midkine减弱淀粉样蛋白-β纤维的组装和斑块的形成

Nature structural & molecular biology Pub Date : 2025-08-21 DOI: 10.1038/s41594-025-01657-8

Masihuz Zaman, Shu Yang, Ya Huang, Jay M. Yarbro, Yanhong Hao, Zhen Wang, Danting Liu, Kiara E. Harper, Hadeer Soliman, Alex Hemphill, Sarah Harvey, Shondra M. Pruett-Miller, Valerie Stewart, Ajay Singh Tanwar, Ravi Kalathur, Christy R. Grace, Martin Turk, Sagar Chittori, Yun Jiao, Zhiping Wu, Anthony A. High, Xusheng Wang, Geidy E. Serrano, Thomas G. Beach, Gang Yu, Yang Yang, Ping-Chung Chen, Junmin Peng

{"title":"Midkine attenuates amyloid-β fibril assembly and plaque formation","authors":"Masihuz Zaman, Shu Yang, Ya Huang, Jay M. Yarbro, Yanhong Hao, Zhen Wang, Danting Liu, Kiara E. Harper, Hadeer Soliman, Alex Hemphill, Sarah Harvey, Shondra M. Pruett-Miller, Valerie Stewart, Ajay Singh Tanwar, Ravi Kalathur, Christy R. Grace, Martin Turk, Sagar Chittori, Yun Jiao, Zhiping Wu, Anthony A. High, Xusheng Wang, Geidy E. Serrano, Thomas G. Beach, Gang Yu, Yang Yang, Ping-Chung Chen, Junmin Peng","doi":"10.1038/s41594-025-01657-8","DOIUrl":"https://doi.org/10.1038/s41594-025-01657-8","url":null,"abstract":"Proteomic profiling of Alzheimer disease (AD) brains has identified numerous understudied proteins, including midkine (MDK), that are highly upregulated and correlated with amyloid-β (Aβ) from the early disease stage but their roles in disease progression are not fully understood. Here, we present that MDK attenuates Aβ assembly and influences amyloid formation in the 5xFAD amyloidosis mouse model. MDK protein mitigates fibril formation of both Aβ40 and Aβ42 peptides according to thioflavin T fluorescence, circular dichroism, negative-stain electron microscopy and nuclear magnetic resonance analyses. Knockout of the Mdk gene in 5xFAD increased amyloid formation and microglial activation in the brain. Further comprehensive mass-spectrometry-based profiling of the whole proteome and detergent-insoluble proteome in these mouse models indicated significant accumulation of Aβ and Aβ-correlated proteins, along with microglial components. Thus, our structural and mouse model studies reveal a protective role of MDK in counteracting amyloid pathology in AD.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0