Structures of vesicular stomatitis virus glycoprotein G alone and in complex with a neutralizing antibody
VSV G mediates viral entry via endocytosis. In the endosome, G undergoes a pH-dependent conformational change from pre- to post-fusion state, catalyzing membrane fusion. So far, no complete structure of G has been reported. We report cryo-EM structures of G, isolated from virions using detergent, alone and in complex with neutralizing antibody FAb that binds G in all conformations. The post-fusion structure reveals novel details about the organization of the C-terminal part of the ectodomain, showing that it undergoes conformational rearrangement and stabilizes the post-fusion trimer by nesting into a groove between adjacent fusion domains. The fusion loops are visible inside the micelle, which is not the case of the transmembrane domains, suggesting that they are rather mobile. Structures of G-FAb complex show that the epitope belongs to a conserved antigenic site. This work has potential implications for vaccine development and oncolytic virotherapy.