发布求助
文献互助 智能选刊 最新文献

Nature structural & molecular biology最新文献

筛选
英文 中文
KIF1C activates and extends dynein movement through the FHF cargo adapter KIF1C通过FHF货运适配器激活并扩展动力蛋白运动
Nature structural & molecular biology Pub Date : 2025-01-02 DOI: 10.1038/s41594-024-01418-z
Ferdos Abid Ali, Alexander J. Zwetsloot, Caroline E. Stone, Tomos E. Morgan, Richard F. Wademan, Andrew P. Carter, Anne Straube
{"title":"KIF1C activates and extends dynein movement through the FHF cargo adapter","authors":"Ferdos Abid Ali, Alexander J. Zwetsloot, Caroline E. Stone, Tomos E. Morgan, Richard F. Wademan, Andrew P. Carter, Anne Straube","doi":"10.1038/s41594-024-01418-z","DOIUrl":"https://doi.org/10.1038/s41594-024-01418-z","url":null,"abstract":"<p>Cellular cargos move bidirectionally on microtubules by recruiting opposite polarity motors dynein and kinesin. These motors show codependence, where one requires the activity of the other, although the mechanism is unknown. Here we show that kinesin-3 KIF1C acts as both an activator and a processivity factor for dynein, using in vitro reconstitutions of human proteins. Activation requires only a fragment of the KIF1C nonmotor stalk binding the cargo adapter HOOK3. The interaction site is separate from the constitutive factors FTS and FHIP, which link HOOK3 to small G-proteins on cargos. We provide a structural model for the autoinhibited FTS–HOOK3–FHIP1B (an FHF complex) and explain how KIF1C relieves it. Collectively, we explain codependency by revealing how mutual activation of dynein and kinesin occurs through their shared adapter. Many adapters bind both dynein and kinesins, suggesting this mechanism could be generalized to other bidirectional complexes.</p>","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911455","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
Molecular basis of human nuclear and mitochondrial tRNA 3′ processing 人类细胞核和线粒体tRNA 3 '加工的分子基础
Nature structural & molecular biology Pub Date : 2025-01-02 DOI: 10.1038/s41594-024-01445-w
Arjun Bhatta, Bernhard Kuhle, Ryan D. Yu, Lucas Spanaus, Katja Ditter, Katherine E. Bohnsack, Hauke S. Hillen
{"title":"Molecular basis of human nuclear and mitochondrial tRNA 3′ processing","authors":"Arjun Bhatta, Bernhard Kuhle, Ryan D. Yu, Lucas Spanaus, Katja Ditter, Katherine E. Bohnsack, Hauke S. Hillen","doi":"10.1038/s41594-024-01445-w","DOIUrl":"https://doi.org/10.1038/s41594-024-01445-w","url":null,"abstract":"<p>Eukaryotic transfer RNA (tRNA) precursors undergo sequential processing steps to become mature tRNAs. In humans, ELAC2 carries out 3′ end processing of both nucleus-encoded (nu-tRNAs) and mitochondria-encoded (mt-tRNAs) tRNAs. ELAC2 is self-sufficient for processing of nu-tRNAs but requires TRMT10C and SDR5C1 to process most mt-tRNAs. Here we show that TRMT10C and SDR5C1 specifically facilitate processing of structurally degenerate mt-tRNAs lacking the canonical elbow. Structures of ELAC2 in complex with TRMT10C, SDR5C1 and two divergent mt-tRNA substrates reveal two distinct mechanisms of pre-tRNA recognition. While canonical nu-tRNAs and mt-tRNAs are recognized by direct ELAC2–RNA interactions, processing of noncanonical mt-tRNAs depends on protein–protein interactions between ELAC2 and TRMT10C. These results provide the molecular basis for tRNA 3′ processing in both the nucleus and the mitochondria and explain the organelle-specific requirement for additional factors. Moreover, they suggest that TRMT10C–SDR5C1 evolved as a mitochondrial tRNA maturation platform to compensate for the structural erosion of mt-tRNAs in bilaterian animals.</p>","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911433","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 of human γ-secretase inhibition by anticancer clinical compounds 抗癌临床化合物抑制人γ-分泌酶的结构基础
Nature structural & molecular biology Pub Date : 2024-12-09 DOI: 10.1038/s41594-024-01439-8
Xuefei Guo, Haotian Li, Xiaoli Lu, Hao Liu, Kaicheng U, Chuangye Yan, Jianlin Lei, Jing Huang, Rui Zhou, Yigong Shi
{"title":"Structural basis of human γ-secretase inhibition by anticancer clinical compounds","authors":"Xuefei Guo, Haotian Li, Xiaoli Lu, Hao Liu, Kaicheng U, Chuangye Yan, Jianlin Lei, Jing Huang, Rui Zhou, Yigong Shi","doi":"10.1038/s41594-024-01439-8","DOIUrl":"https://doi.org/10.1038/s41594-024-01439-8","url":null,"abstract":"<p>Aberrant activation of Notch signaling, mediated by the Notch intracellular domain (NICD), is linked to certain types of cancer. The NICD is released through γ-secretase-mediated cleavage of the Notch receptor. Therefore, development of a γ-secretase inhibitor (GSI) represents an anticancer strategy. Here we report the cryo-electron microscopy structures of human γ-secretase bound individually to five clinically tested GSIs (RO4929097, crenigacestat, BMS906024, nirogacestat and MK-0752) at overall resolutions of 2.4–3.0 Å. Three of the five GSIs are in active anticancer clinical trials, while nirogacestat was recently approved. Each of these GSIs similarly occupies the substrate-binding site of presenilin 1 but shows characteristic differences in detailed recognition pattern. The size and shape of the binding pocket are induced by the bound GSI. Analysis of these structural features suggest strategies for modification of the GSI with improved inhibition potency.</p>","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793554","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
Epitranscriptome regulation. 上皮转录组调控。
Nature structural & molecular biology Pub Date : 2018-09-28 DOI: 10.1038/s41594-018-0140-7
Dan Dominissini, Gideon Rechavi
{"title":"Epitranscriptome regulation.","authors":"Dan Dominissini, Gideon Rechavi","doi":"10.1038/s41594-018-0140-7","DOIUrl":"10.1038/s41594-018-0140-7","url":null,"abstract":"","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36535441","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
Intersubunit capture of regulatory segments is a component of cooperative CaMKII activation. 调控片段的亚基间捕获是CaMKII协同激活的一个组成部分。
Nature structural & molecular biology Pub Date : 2010-03-01 DOI: 10.1038/nsmb.1751
Luke H Chao, Patricia Pellicena, Sebastian Deindl, Lauren A Barclay, Howard Schulman, John Kuriyan
{"title":"Intersubunit capture of regulatory segments is a component of cooperative CaMKII activation.","authors":"Luke H Chao,&nbsp;Patricia Pellicena,&nbsp;Sebastian Deindl,&nbsp;Lauren A Barclay,&nbsp;Howard Schulman,&nbsp;John Kuriyan","doi":"10.1038/nsmb.1751","DOIUrl":"https://doi.org/10.1038/nsmb.1751","url":null,"abstract":"<p><p>The dodecameric holoenzyme of calcium-calmodulin-dependent protein kinase II (CaMKII) responds to high-frequency Ca(2+) pulses to become Ca(2+) independent. A simple coincidence-detector model for Ca(2+)-frequency dependency assumes noncooperative activation of kinase domains. We show that activation of CaMKII by Ca(2+)-calmodulin is cooperative, with a Hill coefficient of approximately 3.0, implying sequential kinase-domain activation beyond dimeric units. We present data for a model in which cooperative activation includes the intersubunit 'capture' of regulatory segments. Such a capture interaction is seen in a crystal structure that shows extensive contacts between the regulatory segment of one kinase and the catalytic domain of another. These interactions are mimicked by a natural inhibitor of CaMKII. Our results show that a simple coincidence-detection model cannot be operative and point to the importance of kinetic dissection of the frequency-response mechanism in future experiments.</p>","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"17 3","pages":"264-72"},"PeriodicalIF":0.0,"publicationDate":"2010-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/nsmb.1751","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9338579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 115
Domain structure of separase and its binding to securin as determined by EM. 分离酶的结构域结构及其与securin的结合。
Nature structural & molecular biology Pub Date : 2005-06-01 Epub Date: 2005-05-08 DOI: 10.1038/nsmb935
Hector Viadiu, Olaf Stemmann, Marc W Kirschner, Thomas Walz
{"title":"Domain structure of separase and its binding to securin as determined by EM.","authors":"Hector Viadiu,&nbsp;Olaf Stemmann,&nbsp;Marc W Kirschner,&nbsp;Thomas Walz","doi":"10.1038/nsmb935","DOIUrl":"https://doi.org/10.1038/nsmb935","url":null,"abstract":"<p><p>After the degradation of its inhibitor securin, separase initiates chromosome segregation during the metaphase-to-anaphase transition by cleaving cohesin. Here we present a density map at a resolution of 25 A of negatively stained separase-securin complex. Based on labeling data and sequence analysis, we propose a model for the structure of separase, consisting of 26 ARM repeats, an unstructured region of 280 residues and two caspase-like domains, with securin binding to the ARM repeats.</p>","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"12 6","pages":"552-3"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/nsmb935","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25271368","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: 51
首页 上一页
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整，为了账户安全，请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们：info@booksci.cn Book学术提供免费学术资源搜索服务，方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号：481959085
Book学术官方微信