Abstract
Structural Virology The 2013–2016 Ebola epidemic in West Africa caused terrible disease and more than 10,000 deaths. The only protein on the surface of this virus is the glycoprotein (GP), which comprises the GP1 and GP2 domains. After binding to a host protein, GP1 is unclamped from GP2, and GP2 initiates membrane fusion that implicates cholesterol. Lee et al. show that cholesterol interacts with glycine residues in the transmembrane domain of GP2. Mutation of a key glycine reduced membrane fusion using GP2 embedded in viral membrane surrogates and reduced cell entry of virus-like particles. Such particles produced from cells treated with cholesterol-lowering statins also showed impaired cell entry. Biophysical studies suggest that cholesterol affects the structure of GP2 and that this in turn may affect the efficiency of membrane fusion. Nat. Struct. Mol. Biol. 10.1038/s41594-020-00548-4 (2021).
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