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TitleAsymmetric recognition of HIV-1 Envelope trimer by V1V2 loop-targeting antibodies.
Journal, issue, pagesElife, Vol. 6, Year 2017
Publish dateMay 26, 2017
AuthorsHaoqing Wang / Harry B Gristick / Louise Scharf / Anthony P West / Rachel P Galimidi / Michael S Seaman / Natalia T Freund / Michel C Nussenzweig / Pamela J Bjorkman /
PubMed AbstractThe HIV-1 envelope (Env) glycoprotein binds to host cell receptors to mediate membrane fusion. The prefusion Env trimer is stabilized by V1V2 loops that interact at the trimer apex. Broadly ...The HIV-1 envelope (Env) glycoprotein binds to host cell receptors to mediate membrane fusion. The prefusion Env trimer is stabilized by V1V2 loops that interact at the trimer apex. Broadly neutralizing antibodies (bNAbs) against V1V2 loops, exemplified by PG9, bind asymmetrically as a single Fab to the apex of the symmetric Env trimer using a protruding CDRH3 to penetrate the Env glycan shield. Here we characterized a distinct mode of V1V2 epitope recognition by the new bNAb BG1 in which two Fabs bind asymmetrically per Env trimer using a compact CDRH3. Comparisons between cryo-EM structures of Env trimer complexed with BG1 (6.2 Å resolution) and PG9 (11.5 Å resolution) revealed a new V1V2-targeting strategy by BG1. Analyses of the EM structures provided information relevant to vaccine design including molecular details for different modes of asymmetric recognition of Env trimer and a binding model for BG1 recognition of V1V2 involving glycan flexibility.
External linksElife / PubMed:28548638 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2 - 11.5 Å
Structure data

EMDB-21204:
BG505 SOSIP in complex with antibodies BG1 and 8ANC195
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-8693, PDB-5viy:
BG505 SOSIP.664 in complex with broadly neutralizing antibodies BG1 and 8ANC195
Method: EM (single particle) / Resolution: 6.2 Å

EMDB-8695, PDB-5vj6:
BG505 SOSIP.664 in complex with broadly neutralizing antibodies PG9 and 8ANC195
Method: EM (single particle) / Resolution: 11.5 Å

PDB-5vvf:
Crystal Structure of 354BG1 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-EDO:
1,2-ETHANEDIOL / Ethylene glycol

ChemComp-HOH:
WATER / Water

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 Env / broadly neutralizing antibodies / cryo-EM / single particle analysis / VIRAL PROTEIN-IMMUNE SYSTEM complex / IMMUNE SYSTEM / HIV / broadly neutralizing antibody

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