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TitleAntibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike.
Journal, issue, pagesCell Rep, Vol. 7, Issue 3, Page 785-795, Year 2014
Publish dateMay 8, 2014
AuthorsLouise Scharf / Johannes F Scheid / Jeong Hyun Lee / Anthony P West / Courtney Chen / Han Gao / Priyanthi N P Gnanapragasam / René Mares / Michael S Seaman / Andrew B Ward / Michel C Nussenzweig / Pamela J Bjorkman /
PubMed AbstractBroadly neutralizing antibodies (bNAbs) to HIV-1 envelope glycoprotein (Env) can prevent infection in animal models. Characterized bNAb targets, although key to vaccine and therapeutic strategies, ...Broadly neutralizing antibodies (bNAbs) to HIV-1 envelope glycoprotein (Env) can prevent infection in animal models. Characterized bNAb targets, although key to vaccine and therapeutic strategies, are currently limited. We defined a new site of vulnerability by solving structures of bNAb 8ANC195 complexed with monomeric gp120 by X-ray crystallography and trimeric Env by electron microscopy. The site includes portions of gp41 and N-linked glycans adjacent to the CD4-binding site on gp120, making 8ANC195 the first donor-derived anti-HIV-1 bNAb with an epitope spanning both Env subunits. Rather than penetrating the glycan shield by using a single variable-region CDR loop, 8ANC195 inserted its entire heavy-chain variable domain into a gap to form a large interface with gp120 glycans and regions of the gp120 inner domain not contacted by other bNAbs. By isolating additional 8ANC195 clonal variants, we identified a more potent variant, which may be valuable for therapeutic approaches using bNAb combinations with nonoverlapping epitopes.
External linksCell Rep / PubMed:24767986 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.13 - 18.7 Å
Structure data

EMDB-2625:
Negative stain reconstruction of 8ANC195 Fab in complex with BG505 SOSIP.664 trimer
Method: EM (single particle) / Resolution: 18.7 Å

PDB-4p9h:
Crystal structure of 8ANC195 Fab in complex with gp120 of 93TH057 HIV-1 and soluble CD4 D1D2
Method: X-RAY DIFFRACTION / Resolution: 3.0 Å

PDB-4p9m:
Crystal structure of 8ANC195 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.13 Å

Chemicals

ChemComp-EPE:
4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID / pH buffer*YM

ChemComp-BEN:
BENZAMIDINE

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-HOH:
WATER

Source
  • Human Immunodeficiency Virus-1
  • homo sapiens (human)
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / IG FOLD / ANTI HIV / ANTIBODY / IMMUNE SYSTEM COMPLEX / VIRAL PROTEIN-IMMUNE SYSTEM complex / IMMUNE SYSTEM

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