6fy3 | pdb_00006fy3

Crystal structure of a V2-directed, RV144 vaccine-like antibody from HIV-1 infection, CAP228-3D, bound to a heterologous V2 peptide

spinqualitylabelsall models 6fy3, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6fy3 is a 6 chain structure with sequence from 9hiv1 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: IGHV5-51 (HUMAN), IGLV6-57 (HUMAN), Env (9HIV1) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The alpha4beta7 integrin is a non-essential HIV-1 adhesion receptor, bound by the gp120 V1V2 domain, facilitating rapid viral dissemination into gut-associated lymphoid tissues. Antibodies blocking this interaction early in infection can improve disease outcome, and V1V2-targeted antibodies were correlated with moderate efficacy reported from the RV144 HIV-1 vaccine trial. Monoclonal alpha4beta7-blocking antibodies recognise two slightly different helical V2 conformations, and current structural data suggests their binding sites are occluded in prefusion envelope trimers. Here, we report cocrystal structures of two alpha4beta7-blocking antibodies from an infected donor complexed with scaffolded V1V2 or V2 peptides. Both antibodies recognised the same helix-coil V2 conformation as RV144 antibody CH58, identifying a frequently sampled alternative conformation of full-length V1V2. In the context of Envelope, this alpha-helical form of V1V2 displays highly exposed alpha4beta7-binding sites, potentially providing a functional role for non-native Envelope on virion or infected cell surfaces in HIV-1 dissemination, pathogenesis, and vaccine design. Common helical V1V2 conformations of HIV-1 Envelope expose the alpha4beta7 binding site on intact virions.,Wibmer CK, Richardson SI, Yolitz J, Cicala C, Arthos J, Moore PL, Morris L Nat Commun. 2018 Oct 26;9(1):4489. doi: 10.1038/s41467-018-06794-x. PMID:30367034 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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