Structure最新文献_第3页

LEDGF interacts with the NID domain of MeCP2 and modulates MeCP2 condensates LEDGF与MeCP2的NID结构域相互作用并调节MeCP2的凝结

IF 5.7 2区生物学

Structure Pub Date : 2024-11-04 DOI: 10.1016/j.str.2024.10.016

Saskia Lesire, Rodrigo Lata, Yannick Hoogvliets, Kune Herrebosch, Paulien Van De Velde, Anouk Speleers, Frauke Christ, Siska Van Belle, Zeger Debyser

{"title":"LEDGF interacts with the NID domain of MeCP2 and modulates MeCP2 condensates","authors":"Saskia Lesire, Rodrigo Lata, Yannick Hoogvliets, Kune Herrebosch, Paulien Van De Velde, Anouk Speleers, Frauke Christ, Siska Van Belle, Zeger Debyser","doi":"10.1016/j.str.2024.10.016","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.016","url":null,"abstract":"Methyl-CpG-binding protein 2 (MeCP2) is a ubiquitously expressed nuclear protein involved in transcriptional regulation and chromatin remodeling. MeCP2 exists in two isoforms, MeCP2 E1 and E2, which share the same functional domains. Loss-of-function mutations in the MeCP2 gene are the main cause of Rett syndrome (RTT). Previous studies identified a complex formation between MeCP2 and lens epithelium derived growth factor (LEDGF), a transcriptional regulator that exists in two isoforms, LEDGF/p75 and LEDGF/p52. Here, we characterized the molecular and functional interaction between MeCP2 and LEDGF. The NCoR interaction domain (NID) domain in MeCP2 is essential for the direct binding to the PWWP-CR1 region of LEDGF. Introduction of R306C, an RTT mutation in the NID of MeCP2, reduced the interaction with LEDGF. Our data reveal mutual inhibition of MeCP2 and LEDGF multimerization due to overlapping binding sites. Aligning with this observation, LEDGF depletion resulted in larger MeCP2 and DNA foci in NIH3T3 cells, suggesting a role for the MeCP2-LEDGF complex in chromatin organization.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"87 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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-function analyses of human TRPV6 ancestral and derived haplotypes 人类 TRPV6 祖先和衍生单倍型的结构功能分析

IF 5.7 2区生物学

Structure Pub Date : 2024-11-04 DOI: 10.1016/j.str.2024.10.018

Arthur Neuberger, Alexey Shalygin, Yury A. Trofimov, Irina I. Veretenenko, Kirill D. Nadezhdin, Nikolay A. Krylov, Thomas Gudermann, Roman G. Efremov, Vladimir Chubanov, Alexander I. Sobolevsky

{"title":"Structure-function analyses of human TRPV6 ancestral and derived haplotypes","authors":"Arthur Neuberger, Alexey Shalygin, Yury A. Trofimov, Irina I. Veretenenko, Kirill D. Nadezhdin, Nikolay A. Krylov, Thomas Gudermann, Roman G. Efremov, Vladimir Chubanov, Alexander I. Sobolevsky","doi":"10.1016/j.str.2024.10.018","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.018","url":null,"abstract":"TRPV6 is a Ca2+ selective channel that mediates calcium uptake in the gut and contributes to the development and progression of human cancers. TRPV6 is represented by the ancestral and derived haplotypes that differ by three non-synonymous polymorphisms, located in the N-terminal ankyrin repeat domain (C157R), S1–S2 extracellular loop (M378V), and C-terminus (M681T). The ancestral and derived haplotypes were proposed to serve as genomic factors causing a different outcome for cancer patients of African ancestry. We solved cryoelectron microscopy (cryo-EM) structures of ancestral and derived TRPV6 in the open and calmodulin (CaM)-bound inactivated states. Neither state shows substantial structural differences caused by the non-synonymous polymorphisms. Functional properties assessed by electrophysiological recordings and Ca2+ uptake measurements, and water and ion permeation evaluated by molecular modeling also appear similar between the haplotypes. Therefore, ancestral and derived TRPV6 have similar structure and function, implying that other factors are responsible for the differences in susceptibility to cancer.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"67 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

High-resolution cryo-EM analysis of a Streptococcus pyogenes M-protein/human plasminogen complex 化脓性链球菌 M 蛋白/人纤溶酶原复合物的高分辨率冷冻电镜分析

IF 5.7 2区生物学

Structure Pub Date : 2024-11-04 DOI: 10.1016/j.str.2024.10.003

Bradley M. Readnour, Sheiny Tjia-Fleck, Nathan R. McCann, Yetunde A. Ayinuola, Francis J. Castellino

引用次数: 0

Tau seeds catalyze fibril-type structures from GFP tau biosensor cells Tau 种子催化 GFP tau 生物传感器细胞形成纤维状结构

IF 5.7 2区生物学

Structure Pub Date : 2024-11-01 DOI: 10.1016/j.str.2024.10.013

Jinliang Wang, Christopher K. Williams, Michael A. DeTure, Shino D. Magaki, Dennis W. Dickson, Harry V. Vinters, Paul M. Seidler

{"title":"Tau seeds catalyze fibril-type structures from GFP tau biosensor cells","authors":"Jinliang Wang, Christopher K. Williams, Michael A. DeTure, Shino D. Magaki, Dennis W. Dickson, Harry V. Vinters, Paul M. Seidler","doi":"10.1016/j.str.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.013","url":null,"abstract":"Fibril-type aggregates of tau occur in Alzheimer’s disease (AD) and dozens of tauopathies. Fibrils catalyze aggregation by prion-like seeding, which in part underlies disease progression. Seeding by recombinant and brain-derived tau fibrils is measured using biosensor cells that express aggregation-prone tau mutants fused with fluorescent reporter proteins. Seeding results in a punctated phenotype that is well established, but evidence that fluorescent tau fusion proteins from biosensor cells assemble into fibril-type structures is lacking. We investigated the effects of seeding on fibril formation by biosensor cells. Fluorescent punctated cell phenotypes that were catalyzed persisted with varying stabilities. Seeded cells bearing punctated phenotypes yielded sarkosyl-insoluble fibrils, although non-seeded cells did not. ImmunoEM of cell-purified fibrils shows that GFP localizes to the proteolytically sensitive fuzzy coat of tau fibrils. The presented data offer compelling evidence that fluorescent puncta are fibril-type aggregates of tau that result from prion-like seeding.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"67 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

GeoNet enables the accurate prediction of protein-ligand binding sites through interpretable geometric deep learning 通过可解释的几何深度学习，GeoNet 可准确预测蛋白质配体结合位点

IF 5.7 2区生物学

Structure Pub Date : 2024-11-01 DOI: 10.1016/j.str.2024.10.011

Jiyun Han, Shizhuo Zhang, Mingming Guan, Qiuyu Li, Xin Gao, Juntao Liu

引用次数: 0

Structural and functional studies of the EGF20-27 region reveal new features of the human Notch receptor important for optimal activation 对 EGF20-27 区域的结构和功能研究揭示了人类 Notch 受体对于最佳激活的新特征

IF 5.7 2区生物学

Structure Pub Date : 2024-11-01 DOI: 10.1016/j.str.2024.10.012

Zhihan Bo, Thomas Rowntree, Steven Johnson, Hilman Nurmahdi, Richard J. Suckling, Johan Hill, Boguslawa Korona, Philip C. Weisshuhn, Devon Sheppard, Yao Meng, Shaoyan Liang, Edward D. Lowe, Susan M. Lea, Christina Redfield, Penny A. Handford

{"title":"Structural and functional studies of the EGF20-27 region reveal new features of the human Notch receptor important for optimal activation","authors":"Zhihan Bo, Thomas Rowntree, Steven Johnson, Hilman Nurmahdi, Richard J. Suckling, Johan Hill, Boguslawa Korona, Philip C. Weisshuhn, Devon Sheppard, Yao Meng, Shaoyan Liang, Edward D. Lowe, Susan M. Lea, Christina Redfield, Penny A. Handford","doi":"10.1016/j.str.2024.10.012","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.012","url":null,"abstract":"The Notch receptor is activated by the Delta/Serrate/Lag-2 (DSL) family of ligands. The organization of the extracellular signaling complex is unknown, although structures of Notch/ligand complexes comprising the ligand-binding region (LBR), and negative regulatory region (NRR) region, have been solved. Here, we investigate the human Notch-1 epidermal growth factor-like (EGF) 20-27 region, located between the LBR and NRR, and incorporating the Abruptex (Ax) region, associated with distinctive Drosophila phenotypes. Our analyses, using crystallography, NMR and small angle X-ray scattering (SAXS), support a rigid, elongated organization for EGF20-27 with the EGF20-21 linkage showing Ca2+-dependent flexibility. In functional assays, Notch-1 variants containing Ax substitutions result in reduced ligand-dependent trans-activation. When cis-JAG1 was expressed, Notch activity differences between WT and Ca2+-binding Ax variants were less marked than seen in the trans-activation assays alone, consistent with disruption of cis-inhibition. These data indicate the importance of Ca2+-stabilized structure and suggest the balance of cis- and trans-interactions explains the effects of Drosophila Ax mutations.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"6 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

T6SS-associated Rhs toxin-encapsulating shells: Structural and bioinformatical insights into bacterial weaponry and self-protection 与 T6SS 相关的 Rhs 毒素包裹壳：从结构和生物信息学角度洞察细菌武器与自我保护

IF 5.7 2区生物学

Structure Pub Date : 2024-10-30 DOI: 10.1016/j.str.2024.10.008

Claudia S. Kielkopf, Mikhail M. Shneider, Petr G. Leiman, Nicholas M.I. Taylor

引用次数: 0

Conformational dynamics of SARS-CoV-2 Omicron spike trimers during fusion activation at single molecule resolution 以单分子分辨率观察 SARS-CoV-2 Omicron 穗状三聚体在融合激活过程中的构象动态

IF 5.7 2区生物学

Structure Pub Date : 2024-10-30 DOI: 10.1016/j.str.2024.10.029

Shuvankar Dey, Purba Pahari, Srija Mukherjee, James B. Munro, Dibyendu Kumar Das

引用次数: 0

Native mass spectrometry prescreening of G protein-coupled receptor complexes for cryo-EM structure determination 用于低温电子显微镜结构测定的 G 蛋白偶联受体复合物的原生质谱预筛选

IF 5.7 2区生物学

Structure Pub Date : 2024-10-28 DOI: 10.1016/j.str.2024.10.004

Donggyun Kim, Weijing Liu, Rosa Viner, Vadim Cherezov

引用次数: 0

Structural insight into rabies virus neutralization revealed by an engineered antibody scaffold 工程抗体支架揭示狂犬病病毒中和的结构奥秘

IF 5.7 2区生物学

Structure Pub Date : 2024-10-28 DOI: 10.1016/j.str.2024.10.002

Ashwini Kedari, Rommel Iheozor-Ejiofor, Petja Salminen, Hasan Uğurlu, Anna R. Mäkelä, Lev Levanov, Olli Vapalahti, Vesa P. Hytönen, Kalle Saksela, Ilona Rissanen

{"title":"Structural insight into rabies virus neutralization revealed by an engineered antibody scaffold","authors":"Ashwini Kedari, Rommel Iheozor-Ejiofor, Petja Salminen, Hasan Uğurlu, Anna R. Mäkelä, Lev Levanov, Olli Vapalahti, Vesa P. Hytönen, Kalle Saksela, Ilona Rissanen","doi":"10.1016/j.str.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.002","url":null,"abstract":"Host-cell entry of the highly pathogenic rabies virus (RABV) is mediated by glycoprotein (G) spikes, which also comprise the primary target for the humoral immune response. RABV glycoprotein (RABV-G) displays several antigenic sites that are targeted by neutralizing monoclonal antibodies (mAbs). In this study, we determined the epitope of a potently neutralizing human mAb, CR57, which we engineered into a diabody format to facilitate crystallization. We report the crystal structure of the CR57 diabody alone at 2.38 Å resolution, and in complex with RABV-G domain III at 2.70 Å resolution. The CR57−RABV-G structure reveals critical interactions at the antigen interface, which target the conserved “KLCGVL” peptide and residues proximal to it on RABV-G. Structural analysis combined with a cell-cell fusion assay demonstrates that CR57 effectively inhibits RABV-G-mediated fusion by obstructing the fusogenic transitions of the spike protein. Altogether, this investigation provides a structural perspective on RABV inhibition by a potently neutralizing human antibody.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"12 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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