Nature Structural & Molecular Biology最新文献_第10页

Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation TOPORS和RNF4的协同SUMO靶向泛素连接酶活性对应激管理和细胞增殖至关重要

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-04-22 DOI: 10.1038/s41594-024-01294-7

Julio C. Y. Liu, Leena Ackermann, Saskia Hoffmann, Zita Gál, Ivo A. Hendriks, Charu Jain, Louise Morlot, Michael H. Tatham, Gian-Luca McLelland, Ronald T. Hay, Michael Lund Nielsen, Thijn Brummelkamp, Peter Haahr, Niels Mailand

{"title":"Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation","authors":"Julio C. Y. Liu, Leena Ackermann, Saskia Hoffmann, Zita Gál, Ivo A. Hendriks, Charu Jain, Louise Morlot, Michael H. Tatham, Gian-Luca McLelland, Ronald T. Hay, Michael Lund Nielsen, Thijn Brummelkamp, Peter Haahr, Niels Mailand","doi":"10.1038/s41594-024-01294-7","DOIUrl":"10.1038/s41594-024-01294-7","url":null,"abstract":"Protein SUMOylation provides a principal driving force for cellular stress responses, including DNA–protein crosslink (DPC) repair and arsenic-induced PML body degradation. In this study, using genome-scale screens, we identified the human E3 ligase TOPORS as a key effector of SUMO-dependent DPC resolution. We demonstrate that TOPORS promotes DPC repair by functioning as a SUMO-targeted ubiquitin ligase (STUbL), combining ubiquitin ligase activity through its RING domain with poly-SUMO binding via SUMO-interacting motifs, analogous to the STUbL RNF4. Mechanistically, TOPORS is a SUMO1-selective STUbL that complements RNF4 in generating complex ubiquitin landscapes on SUMOylated targets, including DPCs and PML, stimulating efficient p97/VCP unfoldase recruitment and proteasomal degradation. Combined loss of TOPORS and RNF4 is synthetic lethal even in unstressed cells, involving defective clearance of SUMOylated proteins from chromatin accompanied by cell cycle arrest and apoptosis. Our findings establish TOPORS as a STUbL whose parallel action with RNF4 defines a general mechanistic principle in crucial cellular processes governed by direct SUMO–ubiquitin crosstalk. Liu et al. reveal that human TOPORS is a SUMO1-selective SUMO-targeted ubiquitin ligase (STUbL). The parallel action of TOPORS and the STUbL RNF4 defines a general mechanistic principle governing pathways driven by direct SUMO–ubiquitin crosstalk.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"31 9","pages":"1355-1367"},"PeriodicalIF":12.5,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01294-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632303","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

Macrophages need to release the proximal brake to degrade cellular corpses 巨噬细胞需要释放近端制动器来降解细胞尸体

IF 16.8 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-04-18 DOI: 10.1038/s41594-024-01305-7

Dimitris Typas

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Future opportunities in solute carrier structural biology 溶质载体结构生物学的未来机遇

IF 16.8 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-04-18 DOI: 10.1038/s41594-024-01271-0

Simon Newstead

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Membrane-embedded machines 膜嵌入式机器

IF 16.8 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-04-18 DOI: 10.1038/s41594-024-01303-9

引用次数: 0

HS-AFM single-molecule structural biology uncovers basis of transporter wanderlust kinetics HS-AFM 单分子结构生物学揭示了转运体徘徊动力学的基础

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-04-17 DOI: 10.1038/s41594-024-01260-3

Yining Jiang, Atsushi Miyagi, Xiaoyu Wang, Biao Qiu, Olga Boudker, Simon Scheuring

{"title":"HS-AFM single-molecule structural biology uncovers basis of transporter wanderlust kinetics","authors":"Yining Jiang, Atsushi Miyagi, Xiaoyu Wang, Biao Qiu, Olga Boudker, Simon Scheuring","doi":"10.1038/s41594-024-01260-3","DOIUrl":"10.1038/s41594-024-01260-3","url":null,"abstract":"The Pyrococcus horikoshii amino acid transporter GltPh revealed, like other channels and transporters, activity mode switching, previously termed wanderlust kinetics. Unfortunately, to date, the basis of these activity fluctuations is not understood, probably due to a lack of experimental tools that directly access the structural features of transporters related to their instantaneous activity. Here, we take advantage of high-speed atomic force microscopy, unique in providing simultaneous structural and temporal resolution, to uncover the basis of kinetic mode switching in proteins. We developed membrane extension membrane protein reconstitution that allows the analysis of isolated molecules. Together with localization atomic force microscopy, principal component analysis and hidden Markov modeling, we could associate structural states to a functional timeline, allowing six structures to be solved from a single molecule, and an inward-facing state, IFSopen-1, to be determined as a kinetic dead-end in the conformational landscape. The approaches presented on GltPh are generally applicable and open possibilities for time-resolved dynamic single-molecule structural biology. Combining high-speed atomic force microscopy (AFM) with localization AFM and principal component analysis, the authors present six structures of a glutamate transporter and associate the conformational states to the molecule’s activity timeline.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"31 8","pages":"1286-1295"},"PeriodicalIF":12.5,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140603972","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

Vimentin filaments integrate low-complexity domains in a complex helical structure 波形蛋白丝在复杂的螺旋结构中整合了低复杂度结构域

IF 16.8 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-04-17 DOI: 10.1038/s41594-024-01261-2

Matthias Eibauer, Miriam S. Weber, Rafael Kronenberg-Tenga, Charlie T. Beales, Rajaa Boujemaa-Paterski, Yagmur Turgay, Suganya Sivagurunathan, Julia Kraxner, Sarah Köster, Robert D. Goldman, Ohad Medalia

{"title":"Vimentin filaments integrate low-complexity domains in a complex helical structure","authors":"Matthias Eibauer, Miriam S. Weber, Rafael Kronenberg-Tenga, Charlie T. Beales, Rajaa Boujemaa-Paterski, Yagmur Turgay, Suganya Sivagurunathan, Julia Kraxner, Sarah Köster, Robert D. Goldman, Ohad Medalia","doi":"10.1038/s41594-024-01261-2","DOIUrl":"10.1038/s41594-024-01261-2","url":null,"abstract":"Intermediate filaments (IFs) are integral components of the cytoskeleton. They provide cells with tissue-specific mechanical properties and are involved in numerous cellular processes. Due to their intricate architecture, a 3D structure of IFs has remained elusive. Here we use cryo-focused ion-beam milling, cryo-electron microscopy and tomography to obtain a 3D structure of vimentin IFs (VIFs). VIFs assemble into a modular, intertwined and flexible helical structure of 40 α-helices in cross-section, organized into five protofibrils. Surprisingly, the intrinsically disordered head domains form a fiber in the lumen of VIFs, while the intrinsically disordered tails form lateral connections between the protofibrils. Our findings demonstrate how protein domains of low sequence complexity can complement well-folded protein domains to construct a biopolymer with striking mechanical strength and stretchability. Using cryo-electron microscopy and integrative modeling, the authors defined the structure of vimentin intermediate filaments, revealing a helical tube built of five protofibrils that enclose a fiber of low-complexity N-terminal domains.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"31 6","pages":"939-949"},"PeriodicalIF":16.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01261-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140603662","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

Author Correction: RNA polymerase II pausing regulates chromatin organization in erythrocytes 作者更正：RNA 聚合酶 II 暂停调节红细胞中的染色质组织

IF 16.8 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-04-17 DOI: 10.1038/s41594-024-01307-5

Andrés Penagos-Puig, Sherlyn Claudio-Galeana, Aura Stephenson-Gussinye, Karina Jácome-López, Amaury Aguilar-Lomas, Xingqi Chen, Rosario Pérez-Molina, Mayra Furlan-Magaril

引用次数: 0

DNA double-strand break–capturing nuclear envelope tubules drive DNA repair DNA双链断裂捕获核膜小管驱动DNA修复

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-04-17 DOI: 10.1038/s41594-024-01286-7

Mitra Shokrollahi, Mia Stanic, Anisha Hundal, Janet N. Y. Chan, Defne Urman, Chris A. Jordan, Anne Hakem, Roderic Espin, Jun Hao, Rehna Krishnan, Philipp G. Maass, Brendan C. Dickson, Manoor P. Hande, Miquel A. Pujana, Razqallah Hakem, Karim Mekhail

{"title":"DNA double-strand break–capturing nuclear envelope tubules drive DNA repair","authors":"Mitra Shokrollahi, Mia Stanic, Anisha Hundal, Janet N. Y. Chan, Defne Urman, Chris A. Jordan, Anne Hakem, Roderic Espin, Jun Hao, Rehna Krishnan, Philipp G. Maass, Brendan C. Dickson, Manoor P. Hande, Miquel A. Pujana, Razqallah Hakem, Karim Mekhail","doi":"10.1038/s41594-024-01286-7","DOIUrl":"10.1038/s41594-024-01286-7","url":null,"abstract":"Current models suggest that DNA double-strand breaks (DSBs) can move to the nuclear periphery for repair. It is unclear to what extent human DSBs display such repositioning. Here we show that the human nuclear envelope localizes to DSBs in a manner depending on DNA damage response (DDR) kinases and cytoplasmic microtubules acetylated by α-tubulin acetyltransferase-1 (ATAT1). These factors collaborate with the linker of nucleoskeleton and cytoskeleton complex (LINC), nuclear pore complex (NPC) protein NUP153, nuclear lamina and kinesins KIF5B and KIF13B to generate DSB-capturing nuclear envelope tubules (dsbNETs). dsbNETs are partly supported by nuclear actin filaments and the circadian factor PER1 and reversed by kinesin KIFC3. Although dsbNETs promote repair and survival, they are also co-opted during poly(ADP-ribose) polymerase (PARP) inhibition to restrain BRCA1-deficient breast cancer cells and are hyper-induced in cells expressing the aging-linked lamin A mutant progerin. In summary, our results advance understanding of nuclear structure–function relationships, uncover a nuclear–cytoplasmic DDR and identify dsbNETs as critical factors in genome organization and stability. Here the authors show that the nucleus undergoes a transient ‘metamorphosis’ within a nuclear–cytoplasmic DNA damage response linked to health and disease. Through this process, the nuclear envelope projects tubules that capture damaged DNA, mediating its repair.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"31 9","pages":"1319-1330"},"PeriodicalIF":12.5,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140603637","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

Molecular basis of Gabija anti-phage supramolecular assemblies 加比亚抗噬菌体超分子组装的分子基础

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-04-16 DOI: 10.1038/s41594-024-01283-w

Xiao-Yuan Yang, Zhangfei Shen, Jiale Xie, Jacelyn Greenwald, Ila Marathe, Qingpeng Lin, Wen Jun Xie, Vicki H. Wysocki, Tian-Min Fu

{"title":"Molecular basis of Gabija anti-phage supramolecular assemblies","authors":"Xiao-Yuan Yang, Zhangfei Shen, Jiale Xie, Jacelyn Greenwald, Ila Marathe, Qingpeng Lin, Wen Jun Xie, Vicki H. Wysocki, Tian-Min Fu","doi":"10.1038/s41594-024-01283-w","DOIUrl":"10.1038/s41594-024-01283-w","url":null,"abstract":"As one of the most prevalent anti-phage defense systems in prokaryotes, Gabija consists of a Gabija protein A (GajA) and a Gabija protein B (GajB). The assembly and function of the Gabija system remain unclear. Here we present cryo-EM structures of Bacillus cereus GajA and GajAB complex, revealing tetrameric and octameric assemblies, respectively. In the center of the complex, GajA assembles into a tetramer, which recruits two sets of GajB dimer at opposite sides of the complex, resulting in a 4:4 GajAB supramolecular complex for anti-phage defense. Further biochemical analysis showed that GajA alone is sufficient to cut double-stranded DNA and plasmid DNA, which can be inhibited by ATP. Unexpectedly, the GajAB displays enhanced activity for plasmid DNA, suggesting a role of substrate selection by GajB. Together, our study defines a framework for understanding anti-phage immune defense by the GajAB complex. The Gabija system constitutes one of the most prevalent anti-phage defense systems and is composed of GajA and GajB. Here, using cryo-EM and biochemistry, the authors show that GajA and GajB form a supramolecular complex with a stoichiometry of 4:4 to promote anti-phage defense.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"31 8","pages":"1243-1250"},"PeriodicalIF":12.5,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556866","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

Structure of the native γ-tubulin ring complex capping spindle microtubules 封闭纺锤体微管的原生γ-微管蛋白环状复合物的结构

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-04-12 DOI: 10.1038/s41594-024-01281-y

Tom Dendooven, Stanislau Yatskevich, Alister Burt, Zhuo A. Chen, Dom Bellini, Juri Rappsilber, John V. Kilmartin, David Barford

{"title":"Structure of the native γ-tubulin ring complex capping spindle microtubules","authors":"Tom Dendooven, Stanislau Yatskevich, Alister Burt, Zhuo A. Chen, Dom Bellini, Juri Rappsilber, John V. Kilmartin, David Barford","doi":"10.1038/s41594-024-01281-y","DOIUrl":"10.1038/s41594-024-01281-y","url":null,"abstract":"Microtubule (MT) filaments, composed of α/β-tubulin dimers, are fundamental to cellular architecture, function and organismal development. They are nucleated from MT organizing centers by the evolutionarily conserved γ-tubulin ring complex (γTuRC). However, the molecular mechanism of nucleation remains elusive. Here we used cryo-electron tomography to determine the structure of the native γTuRC capping the minus end of a MT in the context of enriched budding yeast spindles. In our structure, γTuRC presents a ring of γ-tubulin subunits to seed nucleation of exclusively 13-protofilament MTs, adopting an active closed conformation to function as a perfect geometric template for MT nucleation. Our cryo-electron tomography reconstruction revealed that a coiled-coil protein staples the first row of α/β-tubulin of the MT to alternating positions along the γ-tubulin ring of γTuRC. This positioning of α/β-tubulin onto γTuRC suggests a role for the coiled-coil protein in augmenting γTuRC-mediated MT nucleation. Based on our results, we describe a molecular model for budding yeast γTuRC activation and MT nucleation. Using cryo-electron tomography, Dendooven et al. determined the structure of the native budding yeast γ-tubulin ring complex (γTuRC) capping spindle microtubules and showed that γTuRC adopts an active closed conformation to function as a perfect geometric template for microtubule nucleation.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"31 7","pages":"1134-1144"},"PeriodicalIF":12.5,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01281-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547449","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