title: The Role of the Membrane in the Structure and Biophysical Robustness of the Dengue Virion Envelope.
abstract: The dengue virion is surrounded by an envelope of membrane proteins surrounding a lipid bilayer. We have combined the cryoelectron microscopy structures of the membrane proteins (PDB: 3J27) with a lipid bilayer whose composition is based on lipidomics data for insect cell membranes, to obtain a near-atomic resolution computational model of the envelope of the dengue virion. A coarse-grained molecular dynamics simulation on the microsecond timescale enables analysis of key biophysical properties of the dengue outer envelope. Properties analyzed include area per lipid values (for a spherical virion with a mixed lipid composition), bilayer thickness, and lipid diffusion coefficients. Despite the absence of cholesterol from the lipid bilayer, the virion exhibits biophysical robustness (slow lipid diffusion alongside stable bilayer thickness, virion diameter, and shape) that matches the cholesterol-rich membrane of influenza A, with similarly anomalous diffusion of lipids. Biophysical robustness of the envelope may confer resilience to environmental perturbations.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Tyler
authors.initials: T
authors.lastname: Reddy
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: mark.sansom@bioch.ox.ac.uk.
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D020285:Cryoelectron Microscopy; D062126:Databases, Chemical; D003716:Dengue Virus / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D014759:Viral Envelope Proteins / Q000378:metabolism; D014771:Virion / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D008051:Lipid Bilayers; D014759:Viral Envelope Proteins
keywords: dengue virus; diffusion; lipid bilayer; structure and dynamics; viral envelope
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