HIV gp41 and Ebov GP2 fusion domains play critical roles in membrane fusion during viral cell entry. In order to understand how they promote fusion, we have determined the structures of these FDs and several mutants in different lipid environments and correlated them with their fusion activity. Ultimately these studies are designed to find ways to inhibit viral infectivity. Cholesterol is an important mediator of HIV-mediated fusion [Lai, JMB418:3]. In membranes containing <30% cholesterol, the FD forms an alpha helix, but when cholesterol exceeds 30%, the FD forms beta structure. Interestingly, both forms are fusogenic and the most important parameter that determines fusogenicity is the depth of membrane insertion. The Ebov GP2 FD forms a hydrophobic fist-like loop structure in membranes at fusion pH [Gregory PNAS108:11211]. When two critical hinge residues stabilizing this structure are simultaneously replaced by alanines, the native structure is disrupted and fusion is abrogated.

Control of fusion activities of HIV GP41 and Ebola virus fusion domains by membrane lipids

245th National Meeting (2013)

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