Nature structural & molecular biology最新文献

Structural basis of GluK2 kainate receptor activation by a partial agonist 部分激动剂激活GluK2盐酸盐受体的结构基础

Nature structural & molecular biology Pub Date : 2025-05-29 DOI: 10.1038/s41594-025-01566-w

Guadalupe Segura-Covarrubias, Changping Zhou, Nebojša Bogdanović, Lisa Zhang, Nami Tajima

引用次数: 0

Distinct tau filament folds in human MAPT mutants P301L and P301T 人类MAPT突变体P301L和P301T中不同的tau丝折叠

Nature structural & molecular biology Pub Date : 2025-05-29 DOI: 10.1038/s41594-025-01575-9

Manuel Schweighauser, Yang Shi, Alexey G. Murzin, Holly J. Garringer, Ruben Vidal, Jill R. Murrell, M. Elena Erro, Harro Seelaar, Isidro Ferrer, John C. van Swieten, Bernardino Ghetti, Sjors H. W. Scheres, Michel Goedert

{"title":"Distinct tau filament folds in human MAPT mutants P301L and P301T","authors":"Manuel Schweighauser, Yang Shi, Alexey G. Murzin, Holly J. Garringer, Ruben Vidal, Jill R. Murrell, M. Elena Erro, Harro Seelaar, Isidro Ferrer, John C. van Swieten, Bernardino Ghetti, Sjors H. W. Scheres, Michel Goedert","doi":"10.1038/s41594-025-01575-9","DOIUrl":"https://doi.org/10.1038/s41594-025-01575-9","url":null,"abstract":"Mutations in MAPT, the tau gene, give rise to frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), with abundant filamentous tau inclusions in brain cells. Mutations that encode missense variants of residue P301 are the most common and result in the formation of filamentous inclusions made of mutant four-repeat tau. Here we report the cryo-electron microscopy structures of tau filaments from five individuals belonging to three different families with mutation P301L and from one individual from a family with mutation P301T. A distinct three-lobed tau fold resembling the two-layered fold of Pick’s disease was present in the individuals with P301L tau. Two different tau folds were found in the individual with mutation P301T, the less abundant of which was a variant of the three-lobed fold. The major P301T tau fold was V-shaped, with partial similarity to the four-layered tau folds of corticobasal degeneration and argyrophilic grain disease.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164780","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

Structure and activation of the human autophagy-initiating ULK1C:PI3KC3-C1 supercomplex 人自噬启动ULK1C:PI3KC3-C1超复合体的结构和激活

Nature structural & molecular biology Pub Date : 2025-05-29 DOI: 10.1038/s41594-025-01557-x

Minghao Chen, Thanh N. Nguyen, Xuefeng Ren, Grace Khuu, Annan S. I. Cook, Yuanchang Zhao, Ahmet Yildiz, Michael Lazarou, James H. Hurley

引用次数: 0

A competitive regulatory mechanism of the Chd1 remodeler is integral to distorting nucleosomal DNA Chd1重塑器的竞争性调控机制是扭曲核小体DNA的组成部分

Nature structural & molecular biology Pub Date : 2025-05-28 DOI: 10.1038/s41594-025-01556-y

Ilana M. Nodelman, Heather J. Folkwein, Wesley S. Glime, Jean-Paul Armache, Gregory D. Bowman

引用次数: 0

Akt-phosphorylated UFL1 UFMylates ArpC4 to promote metastasis akt磷酸化的UFL1 ufmylate ArpC4促进转移

Nature structural & molecular biology Pub Date : 2025-05-26 DOI: 10.1038/s41594-025-01576-8

Kailiang Zhao, Hao Hu, Debao Fang, Mingran Xie, Jiasheng Chen, Shan Zhang, Suyun Tang, Mingsheng Wu, Xiaorui Guo, Ning Yu, Bao Yao, Wenli Jiang, Chao Wang, Yide Mei

引用次数: 0

UFMylation of ARPC4 facilitates lamellipodia formation and promotes cancer metastasis ARPC4的ufmy化促进板足形成，促进肿瘤转移

Nature structural & molecular biology Pub Date : 2025-05-26 DOI: 10.1038/s41594-025-01577-7

Miao Wang, Yu-Sheng Cong

引用次数: 0

TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains TRIP12结构揭示了K29键和分支泛素链的HECT E3形成

Nature structural & molecular biology Pub Date : 2025-05-26 DOI: 10.1038/s41594-025-01561-1

Samuel A. Maiwald, Laura A. Schneider, Ronnald Vollrath, Joanna Liwocha, Matthew D. Maletic, Kirby N. Swatek, Monique P. C. Mulder, Brenda A. Schulman

{"title":"TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains","authors":"Samuel A. Maiwald, Laura A. Schneider, Ronnald Vollrath, Joanna Liwocha, Matthew D. Maletic, Kirby N. Swatek, Monique P. C. Mulder, Brenda A. Schulman","doi":"10.1038/s41594-025-01561-1","DOIUrl":"https://doi.org/10.1038/s41594-025-01561-1","url":null,"abstract":"Regulation by ubiquitin depends on E3 ligases forging chains of specific topologies, yet the mechanisms underlying the generation of atypical linkages remain largely elusive. Here we utilize biochemistry, chemistry, and cryo-EM to define the catalytic architecture producing K29 linkages and K29/K48 branches for the human HECT E3 TRIP12. TRIP12 resembles a pincer. One pincer side comprises tandem ubiquitin-binding domains, engaging the proximal ubiquitin to direct its K29 towards the ubiquitylation active site, and selectively capturing a distal ubiquitin from a K48-linked chain. The opposite pincer side—the HECT domain—precisely juxtaposes the ubiquitins to be joined, further ensuring K29 linkage specificity. Comparison to the prior structure visualizing K48-linked chain formation by UBR5 reveals a similar mechanism shared by two human HECT enzymes: parallel features of the E3s, donor and acceptor ubiquitins configure the active site around the targeted lysine, with E3-specific domains buttressing the acceptor for linkage-specific polyubiquitylation.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137155","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

TRIMming centrosomal assemblies 修整中心体组件

Nature structural & molecular biology Pub Date : 2025-05-25 DOI: 10.1038/s41594-025-01549-x

Renata Basto

引用次数: 0

TRIM37 prevents ectopic spindle pole assembly by peptide motif recognition and substrate-dependent oligomerization TRIM37通过肽基序识别和底物依赖性寡聚化防止异位纺锤极组装

Nature structural & molecular biology Pub Date : 2025-05-25 DOI: 10.1038/s41594-025-01562-0

Andrew Bellaart, Amanda Brambila, Jiawei Xu, Francisco Mendez Diaz, Amar Deep, John Anzola, Franz Meitinger, Midori Ohta, Kevin D. Corbett, Arshad Desai, Karen Oegema

{"title":"TRIM37 prevents ectopic spindle pole assembly by peptide motif recognition and substrate-dependent oligomerization","authors":"Andrew Bellaart, Amanda Brambila, Jiawei Xu, Francisco Mendez Diaz, Amar Deep, John Anzola, Franz Meitinger, Midori Ohta, Kevin D. Corbett, Arshad Desai, Karen Oegema","doi":"10.1038/s41594-025-01562-0","DOIUrl":"https://doi.org/10.1038/s41594-025-01562-0","url":null,"abstract":"Tightly controlled duplication of centrosomes, the primary microtubule-organizing centers of animal cells, ensures bipolarity of the mitotic spindle and accurate chromosome segregation. The RING–B-box–coiled coil ubiquitin ligase tripartite motif-containing protein 37 (TRIM37), whose loss is associated with elevated chromosome missegregation and the tumor-prone human developmental disorder Mulibrey nanism, prevents the formation of ectopic spindle poles assembling around structured condensates that contain the centrosomal protein centrobin. Here, we show that TRIM37’s tumor necrosis factor receptor-associated factor (TRAF) domain, which is unique in the extended TRIM family, engages peptide motifs in centrobin to suppress condensate formation. TRIM family proteins form antiparallel coiled-coil dimers with RING–B-box domains at each end. Oligomerization resulting from RING–RING interactions and conformational regulation through B-box 2–B-box 2 interfaces are essential for TRIM37 to suppress centrobin condensate formation. These results indicate that, similar to antiviral TRIM ligases, TRIM37 activation is coupled to detection of oligomerized substrates, facilitated by recognition of specific motifs in the substrate, to enforce ubiquitination-mediated clearance of ectopic centrosomal protein assemblies.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133595","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

Mesoscale regulation of microtubule-organizing centers by the E3 ligase TRIM37 E3连接酶TRIM37对微管组织中心的中尺度调控

Nature structural & molecular biology Pub Date : 2025-05-25 DOI: 10.1038/s41594-025-01540-6

Zhong Y. Yeow, Sonia Sarju, Fang-Chi Chang, Lance Y. Xu, Mark van Breugel, Andrew J. Holland

{"title":"Mesoscale regulation of microtubule-organizing centers by the E3 ligase TRIM37","authors":"Zhong Y. Yeow, Sonia Sarju, Fang-Chi Chang, Lance Y. Xu, Mark van Breugel, Andrew J. Holland","doi":"10.1038/s41594-025-01540-6","DOIUrl":"https://doi.org/10.1038/s41594-025-01540-6","url":null,"abstract":"Centrosomes ensure accurate chromosome segregation during cell division. Although the regulation of centrosome number is well established, less is known about the suppression of noncentrosomal microtubule-organizing centers (ncMTOCs). The E3 ligase TRIM37, implicated in Mulibrey nanism and 17q23-amplified cancers, has emerged as a key regulator of both centrosomes and ncMTOCs. Yet, the mechanism by which TRIM37 achieves enzymatic activation to target these mesoscale structures had thus far remained unknown. Here we elucidate the activation process of TRIM37, unveiling a process that initiates with TRAF domain-directed substrate recognition followed by B-box domain-mediated oligomerization and culminates in RING domain dimerization. Using optogenetics, we demonstrate that the E3 activity of TRIM37 is directly coupled to the assembly state of its substrates, being activated only when centrosomal proteins cluster into higher-order assemblies resembling MTOCs. This regulatory framework provides a mechanistic basis for understanding TRIM37-driven pathologies and echoes the restriction of the human immunodeficiency virus capsid by TRIM5, thus unveiling a conserved activation blueprint among TRIM proteins to control turnover of complexes assembled at the mesoscale level.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"80 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133592","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