Science · 2013 · 709 citations · 64 references
Life SciencesBiologyMolecular BiologyMolecular VirologyStructural BiologyVirologyGlycan StructureGlycan-protein InteractionsMacromolecular AssemblyProtein StructureViral StructureVirus StructureAntibodiesCryo-electron Microscopy ReconstructionCryo-electron Microscopy Structure AnalysisRational Vaccine DesignViral Envelope GlycoproteinsViral Envelope ProteinsViral Envelope StructureViral Glycoproteins
The HIV-1 envelope glycoprotein (Env) trimer contains the receptor binding sites and membrane fusion machinery that introduce the viral genome into the host cell. As the only target for broadly neutralizing antibodies (bnAbs), Env is a focus for rational vaccine design. We present a cryo-electron microscopy reconstruction and structural model of a cleaved, soluble Env trimer (termed BG505 SOSIP.664 gp140) in complex with a CD4 binding site (CD4bs) bnAb, PGV04, at 5.8 angstrom resolution. The structure reveals the spatial arrangement of Env components, including the V1/V2, V3, HR1, and HR2 domains, as well as shielding glycans. The structure also provides insights into trimer assembly, gp120-gp41 interactions, and the CD4bs epitope cluster for bnAbs, which covers a more extensive area and defines a more complex site of vulnerability than previously described.
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