Nature Structural & Molecular Biology最新文献_第2页

Author Correction: The importance of physiological and disease contexts in capturing mRNA modifications 作者更正：生理和疾病背景在捕获mRNA修饰中的重要性。

IF 10.1 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-07-11 DOI: 10.1038/s41594-025-01637-y

Audrey Penning, Jana Jeschke, François Fuks

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Ferlin structures Ferlin结构。

IF 10.1 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-07-09 DOI: 10.1038/s41594-025-01624-3

Suhaila Rahman

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Structure-guided molecular glues 结构导向分子胶

IF 10.1 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-07-09 DOI: 10.1038/s41594-025-01627-0

Antonio R. Cerullo

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Structural basis of RECQL5-induced RNA polymerase II transcription braking and subsequent reactivation recql5诱导RNA聚合酶II转录抑制及随后再激活的结构基础

IF 10.1 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-07-07 DOI: 10.1038/s41594-025-01586-6

Luojia Zhang, Yuliya Gordiyenko, Tomos Morgan, Catarina Franco, Ana Tufegdžić Vidaković, Suyang Zhang

{"title":"Structural basis of RECQL5-induced RNA polymerase II transcription braking and subsequent reactivation","authors":"Luojia Zhang, Yuliya Gordiyenko, Tomos Morgan, Catarina Franco, Ana Tufegdžić Vidaković, Suyang Zhang","doi":"10.1038/s41594-025-01586-6","DOIUrl":"10.1038/s41594-025-01586-6","url":null,"abstract":"Abnormally fast transcription elongation can lead to detrimental consequences such as transcription–replication collisions, altered alternative splicing patterns and genome instability. Therefore, elongating RNA polymerase II (Pol II) requires mechanisms to slow its progression, yet the molecular basis of transcription braking remains unclear. RECQL5 is a DNA helicase that functions as a general elongation factor by slowing down Pol II. Here we report cryo-electron microscopy structures of human RECQL5 bound to multiple transcription elongation complexes. Combined with biochemical analysis, we identify an α-helix of RECQL5 responsible for binding Pol II and slowdown of transcription elongation. We further reveal that the transcription-coupled DNA repair (TCR) complex allows Pol II to overcome RECQL5-induced transcription braking through concerted actions of its translocase activity and competition with RECQL5 for engaging Pol II. Additionally, RECQL5 inhibits TCR-mediated Pol II ubiquitination to prevent activation of the DNA repair pathway. Our results suggest a model in which RECQL5 and the TCR complex coordinately regulate transcription elongation rates to ensure transcription efficiency while maintaining genome stability. Using cryo-electron microscopy and biochemistry, Zhang et al. reveal that the DNA helicase RECQL5 and the transcription-coupled DNA repair complex coordinate to regulate transcription elongation rates and maintain genome stability.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 9","pages":"1731-1740"},"PeriodicalIF":10.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01586-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Publisher Correction: ATM and IRAK1 orchestrate two distinct mechanisms of NF-κB activation in response to DNA damage ATM和IRAK1协调了两种不同的NF-κB激活机制，以响应DNA损伤。

IF 10.1 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-07-07 DOI: 10.1038/s41594-025-01638-x

Elodie Bournique, Ambrocio Sanchez, Sunwoo Oh, Daniel Ghazarian, Alisa L. Mahieu, Lavanya Manjunath, Eirene Ednacot, Pedro Ortega, Selma Masri, Ivan Marazzi, Rémi Buisson

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Structural insights into transcriptional regulation by the helicase RECQL5 解旋酶RECQL5转录调控的结构见解

IF 10.1 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-07-07 DOI: 10.1038/s41594-025-01611-8

Alfredo Jose Florez Ariza, Nicholas Z. Lue, Patricia Grob, Benjamin Kaeser, Jie Fang, Susanne A. Kassube, Eva Nogales

{"title":"Structural insights into transcriptional regulation by the helicase RECQL5","authors":"Alfredo Jose Florez Ariza, Nicholas Z. Lue, Patricia Grob, Benjamin Kaeser, Jie Fang, Susanne A. Kassube, Eva Nogales","doi":"10.1038/s41594-025-01611-8","DOIUrl":"10.1038/s41594-025-01611-8","url":null,"abstract":"Transcription poses a major challenge for genome stability. The RECQL5 helicase helps safeguard genome integrity and is the only member of the human RecQ helicase family that directly binds to RNA polymerase II (Pol II) and affects its progression. While RECQL5 mitigates transcription stress in cells, the molecular mechanism underlying this phenomenon is unclear. Here, we use cryo-electron microscopy to determine the structures of stalled human Pol II elongation complexes (ECs) bound to RECQL5. Our structures reveal the molecular interactions stabilizing RECQL5 binding to the Pol II EC and highlight its role as a transcriptional roadblock. Additionally, we find that, in its nucleotide-free state, RECQL5 twists the downstream DNA in the EC and, upon nucleotide binding, undergoes a conformational change that allosterically induces Pol II toward a post-translocation state. We propose that this mechanism may help restart Pol II elongation and, therefore, contribute to reducing transcription stress. Florez Ariza and Lue et al. use cryo-electron microscopy to investigate how the RECQL5 helicase regulates transcription. Their structural findings suggest that RECQL5 can modulate RNA polymerase II’s translocation state, potentially restarting stalled transcription.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 9","pages":"1721-1730"},"PeriodicalIF":10.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01611-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Structural basis for the synergistic assembly of the snRNA export complex snRNA输出复合物协同组装的结构基础

IF 10.1 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-07-03 DOI: 10.1038/s41594-025-01595-5

Etienne Dubiez, William Garland, Maja Finderup Brask, Elisabetta Boeri Erba, Torben Heick Jensen, Jan Kadlec, Stephen Cusack

{"title":"Structural basis for the synergistic assembly of the snRNA export complex","authors":"Etienne Dubiez, William Garland, Maja Finderup Brask, Elisabetta Boeri Erba, Torben Heick Jensen, Jan Kadlec, Stephen Cusack","doi":"10.1038/s41594-025-01595-5","DOIUrl":"10.1038/s41594-025-01595-5","url":null,"abstract":"The nuclear cap-binding complex (CBC) and its partner Arsenite-Resistance Protein 2 (ARS2) regulate the fate of RNA polymerase II transcripts via mutually exclusive interactions with RNA effectors. One such effector is PHAX, which mediates the nuclear export of U-rich small nuclear RNAs (snRNAs). Here we present the cryo-electron microscopy structure of the human snRNA export complex comprising phosphorylated PHAX, CBC, CRM1–RanGTP and capped RNA. The central region of PHAX bridges CBC to the export factor CRM1–RanGTP, while also reinforcing cap dinucleotide binding. Additionally, PHAX interacts with a distant region of CRM1, facilitating contacts of the essential phosphorylated region of PHAX with the prominent basic surface of RanGTP. CBC engagement within the snRNA export complex is incompatible with its binding to other RNA effectors such as ALYREF or NCBP3. We demonstrate that snRNA export complex formation requires synergistic binding of all its components, which in turn displaces ARS2 from CBC and commits the complex for export. Dubiez and colleagues present a cryo-EM structure of the complex responsible for nuclear export of pre-small nuclear RNAs, comprising CBC–PHAX–CRM1–RanGTP. The structure provides insights into the complex architecture, assembly and target RNA recognition.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 8","pages":"1555-1566"},"PeriodicalIF":10.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01595-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assembly mechanism of the snRNA nuclear export complex snRNA核输出复合体的组装机制

IF 10.1 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-07-03 DOI: 10.1038/s41594-025-01618-1

Yihu Xie, Yi Ren

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SNARE disassembly requires Sec18/NSF side loading 圈套拆卸需要Sec18/NSF侧加载

IF 10.1 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-07-02 DOI: 10.1038/s41594-025-01590-w

Yousuf A. Khan, K. Ian White, Richard A. Pfuetzner, Bharti Singal, Luis Esquivies, Garvey Mckenzie, Fang Liu, Katherine DeLong, Ucheor B. Choi, Elizabeth Montabana, Theresa Mclaughlin, William T. Wickner, Axel T. Brunger

{"title":"SNARE disassembly requires Sec18/NSF side loading","authors":"Yousuf A. Khan, K. Ian White, Richard A. Pfuetzner, Bharti Singal, Luis Esquivies, Garvey Mckenzie, Fang Liu, Katherine DeLong, Ucheor B. Choi, Elizabeth Montabana, Theresa Mclaughlin, William T. Wickner, Axel T. Brunger","doi":"10.1038/s41594-025-01590-w","DOIUrl":"10.1038/s41594-025-01590-w","url":null,"abstract":"SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor) proteins drive membrane fusion at different cell compartments as their core domains zipper into a parallel four-helix bundle. After fusion, these bundles are disassembled by the AAA+ (ATPase associated with diverse cellular activities) protein Sec18/NSF and its adaptor Sec17/α-SNAP to make them available for subsequent rounds of membrane fusion. SNARE domains are often flanked by C-terminal transmembrane or N-terminal domains. Previous structures of the NSF–α-SNAP–SNARE complex revealed binding to the D1 ATPase pore, posing a topological constraint as SNARE transmembrane domains would prevent complete substrate threading as suggested for other AAA+ systems. Using mass spectrometry in yeast cells, we show N-terminal SNARE domain interactions with Sec18, exacerbating this topological issue. We present cryo-electron microscopy (cryo-EM) structures of a yeast SNARE complex, Sec18 and Sec17 in a nonhydrolyzing condition, which show SNARE Sso1 threaded through the D1 and D2 ATPase rings of Sec18, with its folded, N-terminal Habc domain interacting with the D2 ring. This domain does not unfold during Sec18/NSF activity. Cryo-EM structures under hydrolyzing conditions revealed substrate-released and substrate-free states of Sec18 with a coordinated opening in the side of the ATPase rings. Thus, Sec18/NSF operates by substrate side loading and unloading topologically constrained SNARE substrates. Khan et al. show that Sec18 uses both D1 and D2 AAA+ rings cooperatively, opening them laterally for SNARE substrate loading and for subsequent release of SNAREs.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 9","pages":"1708-1720"},"PeriodicalIF":10.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01590-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Structural basis and functional roles for Toll-like receptor binding to Latrophilin in C. elegans development toll样受体与嗜Latrophilin结合在秀丽隐杆线虫发育中的结构基础和功能作用

IF 10.1 1区生物学

Nature Structural & Molecular Biology Pub Date : 2025-06-30 DOI: 10.1038/s41594-025-01592-8

Gabriel Carmona-Rosas, Jingxian Li, Jayson J. Smith, Wioletta I. Nawrocka, Shouqiang Cheng, Elana E. Baltrusaitis, Minglei Zhao, Demet Araç, Paschalis Kratsios, Engin Özkan

{"title":"Structural basis and functional roles for Toll-like receptor binding to Latrophilin in C. elegans development","authors":"Gabriel Carmona-Rosas, Jingxian Li, Jayson J. Smith, Wioletta I. Nawrocka, Shouqiang Cheng, Elana E. Baltrusaitis, Minglei Zhao, Demet Araç, Paschalis Kratsios, Engin Özkan","doi":"10.1038/s41594-025-01592-8","DOIUrl":"10.1038/s41594-025-01592-8","url":null,"abstract":"Latrophilins are conserved adhesion-type G-protein-coupled receptors associated with embryonic defects and lethality. However, their mechanistic roles and ligands in embryogenesis remain unknown. Here, we identified TOL-1, the sole Toll-like receptor in Caenorhabditis elegans, as a ligand for the C. elegans latrophilin, LAT-1. The extracellular lectin domain of LAT-1 directly binds to the second leucine-rich repeat domain of TOL-1. The crystal structure and cryo-electron microscopy density map of the LAT-1–TOL-1 extracellular region complex reveal a one-to-one lectin domain interaction with the convex face of a leucine-rich repeat domain. In C. elegans, endogenous mRNA and protein localization analyses showed mutually exclusive sites of expression, suggesting that in vivo LAT-1–TOL-1 interactions mostly occur in trans. Mutagenesis of key interface residues that disrupt the LAT-1–TOL-1 interaction led to partial lethality and malformed embryos. Thus, TOL-1 binding to LAT-1 represents a receptor–ligand axis essential for animal development. Carmona-Rosas, Li and Smith et al. show that two cell surface receptors, latrophilin and Toll-like receptor, interact in Caenorhabditis elegans and mediate strong roles in early development and morphogenesis.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 9","pages":"1683-1696"},"PeriodicalIF":10.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516019","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