6mzj | pdb_00006mzj

Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer, 2 Fabs bound, sharpened map

Loading... Status: waiting for Mol* initialization Structural highlights 6mzj is a 7 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. Ligands: BMA, MAN, NAG NonStd Res: PCA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed VRC01 broadly neutralizing antibodies (bnAbs) target the CD4-binding site (CD4BS) of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env). Unlike mature antibodies, corresponding VRC01 germline precursors poorly bind to Env. Immunogen design has mostly relied on glycan removal from trimeric Env constructs and has had limited success in eliciting mature VRC01 bnAbs. To better understand elicitation of such bnAbs, we characterized the inferred germline precursor of VRC01 in complex with a modified trimeric 426c Env by cryo-electron microscopy and a 426c gp120 core by X-ray crystallography, biolayer interferometry, immunoprecipitation, and glycoproteomics. Our results show VRC01 germline antibodies interacted with a wild-type 426c core lacking variable loops 1-3 in the presence and absence of a glycan at position Asn276, with the latter form binding with higher affinity than the former. Interactions in the presence of an Asn276 oligosaccharide could be enhanced upon carbohydrate shortening, which should be considered for immunogen design. Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer and a glycosylated HIV-1 gp120 core.,Borst AJ, Weidle CE, Gray MD, Frenz B, Snijder J, Joyce MG, Georgiev IS, Stewart-Jones GB, Kwong PD, McGuire AT, DiMaio F, Stamatatos L, Pancera M, Veesler D Elife. 2018 Nov 7;7. pii: 37688. doi: 10.7554/eLife.37688. PMID:30403372 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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