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Entropic Forces Drive Clustering and Spatial Localization of Influenza A M2 During Viral Budding

Madsen, Jesper J., Grimes, J.A., Rossman, Jeremy S., Voth, Gregory 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). E8595-E8603. ISSN 0027-8424. (doi:10.1073/pnas.1805443115) (KAR id:68500)

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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 in order 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.

Item Type: Article
DOI/Identification number: 10.1073/pnas.1805443115
Uncontrolled keywords: budding, membrane curvature, protein clustering, wedging mechanism, lipid-phase behavior
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Jeremy Rossman
Date Deposited: 06 Aug 2018 09:28 UTC
Last Modified: 10 Dec 2022 12:01 UTC
Resource URI: (The current URI for this page, for reference purposes)
Rossman, Jeremy S.:
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