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

Glycerol mediates crosstalk between metabolism and trafficking through the golgin Imh1 甘油通过golgin Imh1介导代谢和运输之间的串扰

Nature structural & molecular biology Pub Date : 2025-07-08 DOI: 10.1038/s41594-025-01600-x

Wan-Yun Chiu, Yi-Hsun Wang, Ming-Chieh Lin, Chun-Chi Lai, Chia-Jung Yu, Fang-Jen S. Lee

引用次数: 0

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

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":"https://doi.org/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.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"108 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568947","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

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

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

引用次数: 0

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

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

引用次数: 0

Returning home: fostering growth of Brazilian research 回国：促进巴西科研的发展

Nature structural & molecular biology Pub Date : 2025-07-03 DOI: 10.1038/s41594-025-01609-2

Sandra M. G. Dias

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

Nature structural & molecular biology Pub Date : 2025-07-03 DOI: 10.1038/s41594-025-01618-1

Yihu Xie, Yi Ren

引用次数: 0

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

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":"https://doi.org/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.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533901","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

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

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":"https://doi.org/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.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"14 7 1","pages":""},"PeriodicalIF":0.0,"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":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

Mechanisms for licensing origins of DNA replication in eukaryotic cells 真核细胞DNA复制起源许可机制

Nature structural & molecular biology Pub Date : 2025-06-30 DOI: 10.1038/s41594-025-01587-5

Bruce Stillman, John F. X. Diffley, Janet H. Iwasa

引用次数: 0

Cell cycle regulation has shaped replication origins in budding yeast 细胞周期调节在出芽酵母中形成了复制起源

Nature structural & molecular biology Pub Date : 2025-06-30 DOI: 10.1038/s41594-025-01591-9

Chew Theng Lim, Thomas C. R. Miller, Kang Wei Tan, Saurabh Talele, Anne Early, Philip East, Humberto Sánchez, Nynke H. Dekker, Alessandro Costa, John F. X. Diffley

{"title":"Cell cycle regulation has shaped replication origins in budding yeast","authors":"Chew Theng Lim, Thomas C. R. Miller, Kang Wei Tan, Saurabh Talele, Anne Early, Philip East, Humberto Sánchez, Nynke H. Dekker, Alessandro Costa, John F. X. Diffley","doi":"10.1038/s41594-025-01591-9","DOIUrl":"https://doi.org/10.1038/s41594-025-01591-9","url":null,"abstract":"Eukaryotic DNA replication initiates from genomic loci known as origins. At budding yeast origins like ARS1, a double hexamer (DH) of the MCM replicative helicase is assembled by origin recognition complex (ORC), Cdc6 and Cdt1 by sequential hexamer loading from two opposed ORC binding sites. Cyclin-dependent kinase (CDK) inhibits DH assembly, which prevents re-replication by restricting helicase loading to the G1 phase. Here, we show that an intrinsically disordered region (IDR) in the Orc2 subunit promotes interaction between ORC and the first loaded, closed-ring MCM hexamer (the MCM–ORC (MO) intermediate). CDK-dependent phosphorylation of this IDR blocks MO formation and DH assembly. We show that MO stabilizes ORC at lower-affinity binding sites required for second hexamer loading. Origins comprising two high-affinity ORC sites can assemble DH efficiently without MO by independently loading single hexamers. Strikingly, these origins escape CDK inhibition in vitro and in vivo. Our work reveals mechanistic plasticity in MCM loading with implications for understanding how CDK regulation has shaped yeast origin evolution and how natural, strong origins might escape cell cycle regulation. We also identify key steps common to loading pathways, with implications for understanding how MCM is loaded in other eukaryotes.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"152 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144516134","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