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. No complete structure of G has been reported so far. We present cryo-EM structures of G, isolated from virions using detergent, alone and in complex with the broadly neutralizing antibody 8G5F1 that binds all G conformations. The post-fusion structure reveals a novel rearrangement of the C-terminal part of the G ectodomain, showing that it undergoes a conformational rearrangement and stabilizes the post-fusion trimer by nesting into a groove between adjacent fusion domains. Structures of G-Fab complex show that the epitope belongs to a conserved antigenic site, explaining the broad neutralization capacity of the antibody. This work provides insights into the molecular basis of VSV G mediated fusion and antibody recognition, with potential implications for vaccine development, oncolytic virotherapy.
Copyright: © 2025 Minoves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.