Nature structural & molecular biology最新文献_第7页

Structural insights into CXCR4 modulation and oligomerization 对 CXCR4 调制和寡聚化的结构见解

Nature structural & molecular biology Pub Date : 2024-09-23 DOI: 10.1038/s41594-024-01397-1

Kei Saotome, Luke L. McGoldrick, Jo-Hao Ho, Trudy F. Ramlall, Sweta Shah, Michael J. Moore, Jee Hae Kim, Raymond Leidich, William C. Olson, Matthew C. Franklin

{"title":"Structural insights into CXCR4 modulation and oligomerization","authors":"Kei Saotome, Luke L. McGoldrick, Jo-Hao Ho, Trudy F. Ramlall, Sweta Shah, Michael J. Moore, Jee Hae Kim, Raymond Leidich, William C. Olson, Matthew C. Franklin","doi":"10.1038/s41594-024-01397-1","DOIUrl":"https://doi.org/10.1038/s41594-024-01397-1","url":null,"abstract":"Activation of the chemokine receptor CXCR4 by its chemokine ligand CXCL12 regulates diverse cellular processes. Previously reported crystal structures of CXCR4 revealed the architecture of an inactive, homodimeric receptor. However, many structural aspects of CXCR4 remain poorly understood. Here, we use cryo-electron microscopy to investigate various modes of human CXCR4 regulation. CXCL12 activates CXCR4 by inserting its N terminus deep into the CXCR4 orthosteric pocket. The binding of US Food and Drug Administration-approved antagonist AMD3100 is stabilized by electrostatic interactions with acidic residues in the seven-transmembrane-helix bundle. A potent antibody blocker, REGN7663, binds across the extracellular face of CXCR4 and inserts its complementarity-determining region H3 loop into the orthosteric pocket. Trimeric and tetrameric structures of CXCR4 reveal modes of G-protein-coupled receptor oligomerization. We show that CXCR4 adopts distinct subunit conformations in trimeric and tetrameric assemblies, highlighting how oligomerization could allosterically regulate chemokine receptor function.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"203 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276833","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

Catalytic and noncatalytic functions of DNA polymerase κ in translesion DNA synthesis DNA 聚合酶 κ 在转座子 DNA 合成中的催化和非催化功能

Nature structural & molecular biology Pub Date : 2024-09-19 DOI: 10.1038/s41594-024-01395-3

Selene Sellés-Baiget, Sara M. Ambjørn, Alberto Carli, Ivo A. Hendriks, Irene Gallina, Norman E. Davey, Bente Benedict, Alessandra Zarantonello, Sampath A. Gadi, Bob Meeusen, Emil P. T. Hertz, Laura Slappendel, Daniel Semlow, Shana Sturla, Michael L. Nielsen, Jakob Nilsson, Thomas C. R. Miller, Julien P. Duxin

{"title":"Catalytic and noncatalytic functions of DNA polymerase κ in translesion DNA synthesis","authors":"Selene Sellés-Baiget, Sara M. Ambjørn, Alberto Carli, Ivo A. Hendriks, Irene Gallina, Norman E. Davey, Bente Benedict, Alessandra Zarantonello, Sampath A. Gadi, Bob Meeusen, Emil P. T. Hertz, Laura Slappendel, Daniel Semlow, Shana Sturla, Michael L. Nielsen, Jakob Nilsson, Thomas C. R. Miller, Julien P. Duxin","doi":"10.1038/s41594-024-01395-3","DOIUrl":"https://doi.org/10.1038/s41594-024-01395-3","url":null,"abstract":"Translesion DNA synthesis (TLS) is a cellular process that enables the bypass of DNA lesions encountered during DNA replication and is emerging as a primary target of chemotherapy. Among vertebrate DNA polymerases, polymerase κ (Polκ) has the distinctive ability to bypass minor groove DNA adducts in vitro. However, Polκ is also required for cells to overcome major groove DNA adducts but the basis of this requirement is unclear. Here, we combine CRISPR base-editor screening technology in human cells with TLS analysis of defined DNA lesions in Xenopus egg extracts to unravel the functions and regulations of Polκ during lesion bypass. Strikingly, we show that Polκ has two main functions during TLS, which are differentially regulated by Rev1 binding. On the one hand, Polκ is essential to replicate across a minor groove DNA lesion in a process that depends on PCNA ubiquitylation but is independent of Rev1. On the other hand, through its cooperative interaction with Rev1 and ubiquitylated PCNA, Polκ appears to stabilize the Rev1–Polζ extension complex on DNA to allow extension past major groove DNA lesions and abasic sites, in a process that is independent of Polκ’s catalytic activity. Together, our work identifies catalytic and noncatalytic functions of Polκ in TLS and reveals important regulatory mechanisms underlying the unique domain architecture present at the C-terminal end of Y-family TLS polymerases.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245303","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

Pseudouridine guides germline small RNA transport and epigenetic inheritance 伪尿嘧啶引导种系小 RNA 运输和表观遗传

Nature structural & molecular biology Pub Date : 2024-09-06 DOI: 10.1038/s41594-024-01392-6

Rowan P. Herridge, Jakub Dolata, Valentina Migliori, Cristiane de Santis Alves, Filipe Borges, Andrea J. Schorn, Frédéric van Ex, Ann Lin, Mateusz Bajczyk, Jean-Sebastien Parent, Tommaso Leonardi, Alan Hendrick, Tony Kouzarides, Robert A. Martienssen

{"title":"Pseudouridine guides germline small RNA transport and epigenetic inheritance","authors":"Rowan P. Herridge, Jakub Dolata, Valentina Migliori, Cristiane de Santis Alves, Filipe Borges, Andrea J. Schorn, Frédéric van Ex, Ann Lin, Mateusz Bajczyk, Jean-Sebastien Parent, Tommaso Leonardi, Alan Hendrick, Tony Kouzarides, Robert A. Martienssen","doi":"10.1038/s41594-024-01392-6","DOIUrl":"https://doi.org/10.1038/s41594-024-01392-6","url":null,"abstract":"Developmental epigenetic modifications in plants and animals are mostly reset during gamete formation but some are inherited from the germline. Small RNAs guide these epigenetic modifications but how inherited small RNAs are distinguished in plants and animals is unknown. Pseudouridine (Ψ) is the most abundant RNA modification but has not been explored in small RNAs. Here, we develop assays to detect Ψ in short RNA sequences, demonstrating its presence in mouse and Arabidopsis microRNAs. Germline small RNAs, namely epigenetically activated small interfering RNAs (easiRNAs) in Arabidopsis pollen and Piwi-interacting RNAs in mouse testes, are enriched for Ψ. In pollen, pseudouridylated easiRNAs are transported to sperm cells from the vegetative nucleus, and PAUSED/HEN5 (PSD), the plant homolog of Exportin-t, interacts genetically with Ψ and is required for this transport. We further show that Exportin-t is required for the triploid block: small RNA dosage-dependent seed lethality that is epigenetically inherited from pollen. Thus, Ψ has a conserved role in marking inherited small RNAs in the germline.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"380 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142436","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

Distinct stabilization of the human T cell leukemia virus type 1 immature Gag lattice 人类 T 细胞白血病病毒 1 型未成熟 Gag 网格的独特稳定性

Nature structural & molecular biology Pub Date : 2024-09-06 DOI: 10.1038/s41594-024-01390-8

Martin Obr, Mathias Percipalle, Darya Chernikova, Huixin Yang, Andreas Thader, Gergely Pinke, Dario Porley, Louis M. Mansky, Robert A. Dick, Florian K. M. Schur

引用次数: 0

The cyanobacterial protein VIPP1 forms ESCRT-III-like structures on lipid bilayers 蓝藻蛋白 VIPP1 在脂质双分子层上形成类似 ESCRT-III 的结构

Nature structural & molecular biology Pub Date : 2024-07-26 DOI: 10.1038/s41594-024-01367-7

Sichen Pan, Karin Gries, Benjamin D. Engel, Michael Schroda, Christoph A. Haselwandter, Simon Scheuring

{"title":"The cyanobacterial protein VIPP1 forms ESCRT-III-like structures on lipid bilayers","authors":"Sichen Pan, Karin Gries, Benjamin D. Engel, Michael Schroda, Christoph A. Haselwandter, Simon Scheuring","doi":"10.1038/s41594-024-01367-7","DOIUrl":"https://doi.org/10.1038/s41594-024-01367-7","url":null,"abstract":"The biogenesis and maintenance of thylakoid membranes require vesicle-inducing protein in plastids 1 (VIPP1). VIPP1 is a member of the endosomal sorting complex required for transport-III (ESCRT-III) superfamily, whose members form diverse filament-based supramolecular structures that facilitate membrane deformation and fission. VIPP1 cryo-electron microscopy (EM) structures in solution revealed helical rods and baskets of stacked rings, with amphipathic membrane-binding domains in the lumen. However, how VIPP1 interacts with membranes remains largely unknown. Here, using high-speed atomic force microscopy (HS-AFM), we show that VIPP1 assembles into right-handed chiral spirals and regular polygons on supported lipid bilayers via ESCRT-III-like filament assembly and dynamics. VIPP1 filaments grow clockwise into spirals through polymerization at a ring-shaped central polymerization hub, and into polygons through clockwise polymerization at the sector peripheries. Interestingly, VIPP1 initially forms Archimedean spirals, which upon maturation transform into logarithmic spirals through lateral annealing of strands to the outermore low-curvature spiral turns.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764278","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

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

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

引用次数: 51