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DOI | 10.1073/pnas.1805443115 |
Entropic forces drive clustering and spatial localization of influenza A M2 during viral budding | |
Madsen J.J.; Grime J.M.A.; Rossman J.S.; Voth G.A. | |
发表日期 | 2018 |
ISSN | 0027-8424 |
起始页码 | E8595 |
结束页码 | E8603 |
卷号 | 115期号:37 |
英文摘要 | The influenza A matrix 2 (M2) transmembrane protein facilitates virion release from the infected host cell. In particular, M2 plays a role in the induction of membrane curvature and/or in the scission process whereby the envelope is cut upon virion release. Here we show using coarse-grained computer simulations that various M2 assembly geometries emerge due to an entropic driving force, resulting in compact clusters or linearly extended aggregates as a direct consequence of the lateral membrane stresses. Conditions under which these protein assemblies will cause the lipid membrane to curve are explored, and we predict that a critical cluster size is required for this to happen. We go on to demonstrate that under the stress conditions taking place in the cellular membrane as it undergoes large-scale membrane remodeling, the M2 protein will, in principle, be able to both contribute to curvature induction and sense curvature to line up in manifolds where local membrane line tension is high. M2 is found to exhibit linactant behavior in liquid-disordered–liquid-ordered phase-separated lipid mixtures and to be excluded from the liquid-ordered phase, in near-quantitative agreement with experimental observations. Our findings support a role for M2 in membrane remodeling during influenza viral budding both as an inducer and a sensor of membrane curvature, and they suggest a mechanism by which localization of M2 can occur as the virion assembles and releases from the host cell, independent of how the membrane curvature is produced. © 2018 National Academy of Sciences. All Rights Reserved. |
英文关键词 | Budding; Lipid-phase behavior; Membrane curvature; Protein clustering; Wedging mechanism |
语种 | 英语 |
scopus关键词 | protein M2; M2 protein, Influenza A virus; matrix protein; membrane lipid; Article; biological model; cluster analysis; computer model; controlled study; entropy; force; host cell; Influenza A virus; lipid membrane; mechanical stress; membrane structure; prediction; priority journal; protein aggregation; protein folding; protein function; protein localization; quantitative analysis; simulation; virion; virus release; algorithm; animal; cell membrane; chemistry; dog; electron microscopy; host pathogen interaction; MDCK cell line; molecular dynamics; physiology; ultrastructure; virology; virus assembly; Algorithms; Animals; Cell Membrane; Dogs; Entropy; Host-Pathogen Interactions; Madin Darby Canine Kidney Cells; Membrane Lipids; Microscopy, Electron; Models, Biological; Molecular Dynamics Simulation; Viral Matrix Proteins; Virus Assembly; Virus Release |
来源期刊 | Proceedings of the National Academy of Sciences of the United States of America |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/160468 |
作者单位 | Madsen, J.J., Department of Chemistry, University of Chicago, Chicago, IL 60637, United States, James Franck Institute, University of Chicago, Chicago, IL 60637, United States, Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, United States; Grime, J.M.A., Department of Chemistry, University of Chicago, Chicago, IL 60637, United States, James Franck Institute, University of Chicago, Chicago, IL 60637, United States, Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, United States; Rossman, J.S., School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, United Kingdom; Voth, G.A., Department of Chemistry, University of Chicago, Chicago, IL 60637, United States, James Franck Institute, University of Chicago, Chicago, IL 60637, United States, Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, United States |
推荐引用方式 GB/T 7714 | Madsen J.J.,Grime J.M.A.,Rossman J.S.,et al. Entropic forces drive clustering and spatial localization of influenza A M2 during viral budding[J],2018,115(37). |
APA | Madsen J.J.,Grime J.M.A.,Rossman J.S.,&Voth G.A..(2018).Entropic forces drive clustering and spatial localization of influenza A M2 during viral budding.Proceedings of the National Academy of Sciences of the United States of America,115(37). |
MLA | Madsen J.J.,et al."Entropic forces drive clustering and spatial localization of influenza A M2 during viral budding".Proceedings of the National Academy of Sciences of the United States of America 115.37(2018). |
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