Structural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage Antibody affinity maturation enables adaptive immune responses to a wide range of pathogens. In some individuals broadly neutralizing antibodies develop to recognize rapidly mutating pathogens with extensive sequence diversity. Vaccine design for pathogens such as HIV-1 and influenza has therefore focused on recapitulating the natural…
Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. We describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive neutralizing Abs in HIV-1 vaccinated and simian-HIV (SHIV)-infected…
Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements The trimeric HIV-1 Envelope protein (Env) mediates viral-host cell fusion via a network of conformational transitions, with allosteric elements in each protomer orchestrating host receptor-induced exposure of the co-receptor binding site and fusion elements. To understand the molecular details of this allostery, here, we introduce Env mutations aimed to…
Prefusion Structure of Trimeric HIV-1 Envelope Glycoprotein Determined by Cryo-Electron Microscopy HIV-1 Env transitions from a closed to an open state upon binding to its cellular receptor. Single-particle cryo-EM analysis now reveals the closed state of the HIV-1 Env trimer at ~6-Å resolution, featuring three gp41 helices at the center of the trimer. These findings indicate that HIV-1 enters…
Molecular Architectures of Trimeric SIV and HIV-1 Envelope Glycoproteins on Intact Viruses: Strain-Dependent Variation in Quaternary Structure HIV and SIV contact and infect target T-cells following the binding of trimeric Env spikes displayed on the viral membrane with cellular receptors. The conformational changes in trimeric Env that are triggered by the interaction between trimeric Env and cell surface receptors…
Molecular Architecture of Native HIV-1 gp120 Trimers We determined the structure of the native gp120 coat protein of HIV by cryo-electron tomography and molecular modelling. Comparison of gp120 structures in an unbound state, bound to a neutralizing antibody and bound to CD4 cell surface protein provides insight into the conformational changes that occur during antibody neutralization and attachment to…
