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bioRxiv · 10.1101/2025.04.18.649534

SARS-CoV E protein couples asymmetric leaflet thickness and curvature deformations

Sandberg, J. W.·Brannigan, G.
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Abstract

The Envelope protein (E protein) of SARS-CoVs 1 and 2 has been implicated in the viral budding process and maintaining the spherical shape of the virus, but direct evidence linking the protein to long-range membrane deformation is still lacking. Computational predictions from molecular simulation have offered conflicting results, some showing long-range E-induced membrane curvature and others showing only local deformations. In the present study, we determine the mechanism driving these deformations by modulating the degree of hydrophobic mismatch between protein and membrane. We observe that certain barostat and restraint settings, common in coarse-grained MD simulations, can prevent equilibration of the membrane area. Our results indicate that the E protein does not induce long-range curvature, but does exhibit severe local deformations that are exacerbated by hydrophobic mismatch. These deformations occur in conjunction with local leaflet thickness asymmetry, suggesting asymmetry and curvature couple to reduce the free energy cost of a deformed membrane. HighlightsO_LIE protein pentamers from SARS-CoV-1 and SARS-CoV-2 do not induce long-range curvature in membranes when simulated in isolation. C_LIO_LIPrevious findings documenting long-range membrane deformation may reflect the use of restraint and barostat settings that trap the membrane in a compressed state. C_LIO_LIE proteins induce large, asymmetric membrane deformations local to the protein, but these deformations do not propagate into the bulk. C_LIO_LIMembrane leaflet thickness asymmetry may be non-negligible around proteins that are not cylindrical. C_LIO_LIMembrane leaflet thickness asymmetry and mean curvature couple to alleviate free energy cost of deformation. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/649534v2_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@196eec7org.highwire.dtl.DTLVardef@168b3borg.highwire.dtl.DTLVardef@eef5corg.highwire.dtl.DTLVardef@848526_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Sandberg, J. W., Brannigan, G.. 2025-04-22. SARS-CoV E protein couples asymmetric leaflet thickness and curvature deformations. https://doi.org/10.1101/2025.04.18.649534

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