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Influenza A M2 Channel Clustering at High Protein/Lipid Ratios: Viral Budding Implications

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  • Influenza A M2 Channel Clustering at High Protein/Lipid Ratios: Viral Budding Implications

    Biophys J. 2019 Feb 10. pii: S0006-3495(19)30114-6. doi: 10.1016/j.bpj.2019.01.042. [Epub ahead of print]
    Influenza A M2 Channel Clustering at High Protein/Lipid Ratios: Viral Budding Implications.

    Paulino J1, Pang X2, **** I3, Zhou HX4, Cross TA5.
    Author information

    Abstract

    Protein dynamics in crowded environments is important for understanding protein functions in vivo and is especially relevant for membrane proteins because of the roles of protein-protein interactions in membrane protein functions and their regulation. Here, using solid-state NMR spectroscopy in combination with coarse-grained molecular dynamics simulations, we report that the rotational correlation time for the transmembrane domain of the influenza A M2 proton channel in lipid bilayers increases dramatically at an elevated protein/lipid ratio. This increase is attributable to persistent protein-protein interactions, thus revealing for the first time, to the best of our knowledge, extensive cluster formation of the M2 tetrameric channel. Such clustering appears to have direct biological relevance during budding of the nascent influenza virus, which does not use the endosomal sorting complexes required for transport machinery. Indeed, initial coarse-grained molecular dynamics simulations of the longer M2 construct known as the conductance domain suggest clustering-induced membrane curvature formation.
    Copyright ? 2019 Biophysical Society. All rights reserved.


    PMID: 30819568 DOI: 10.1016/j.bpj.2019.01.042
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