Prefusion structure of trimeric HIV-1 envelope glycoprotein determined by cryo-electron microscopy

Abstract

The activation of trimeric HIV-1 envelope glycoprotein (Env) by its binding to the cell surface receptor CD4 and co-receptors (CCR5 or CXCR4) represents the first of a series of events that lead to fusion between viral and target cell membranes. Here, we present the cryo-electron microscopic structure, at ~ 6 Å resolution, of the closed, pre-fusion state of trimeric HIV-1 Env in complex with the broadly neutralizing antibody VRC03. We show that three gp41 helices at the core of the trimer serve as an anchor around which the rest of Env is reorganized upon activation to the open quaternary conformation. The architecture of trimeric HIV-1 Env in pre-fusion and activated intermediate states resembles the corresponding states of influenza hemagglutinin trimers, providing direct evidence for the similarity in entry mechanisms employed by HIV-1, influenza and related enveloped viruses.