Capturing intermediates and membrane remodeling in class III viral fusion.

ABSTRACT: Enveloped viruses enter cells by fusing their envelopes to host cell membranes. Vesicular stomatitis virus (VSV) glycoprotein (G) is a prototype for class III fusion proteins. Although structures of the stable pre- and postfusion ectodomain of G are known, its fusogenic intermediates are insufficiently characterized. Here, we incubated VSV virions with late endosome-mimicking liposomes at pH 5.5 and used cryo-electron tomography (cryo-ET) to visualize stages of VSV's membrane fusion pathway, capture refolding intermediates of G, and reconstruct a sequence of G conformational changes. We observe that the G trimer disassembles into monomers and parallel dimers that explore a broad conformational space. Extended intermediates engage target membranes and mediate fusion, resulting in viral unco

SUBMITTER: Milojevic L 

PROVIDER: S-EPMC11616707 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature