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TitleAntibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike.
Journal, issue, pagesNat Commun, Vol. 6, Page 8167, Year 2015
Publish dateSep 25, 2015
AuthorsJeong Hyun Lee / Daniel P Leaman / Arthur S Kim / Alba Torrents de la Peña / Kwinten Sliepen / Anila Yasmeen / Ronald Derking / Alejandra Ramos / Steven W de Taeye / Gabriel Ozorowski / Florian Klein / Dennis R Burton / Michel C Nussenzweig / Pascal Poignard / John P Moore / Per Johan Klasse / Rogier W Sanders / Michael B Zwick / Ian A Wilson / Andrew B Ward /
PubMed AbstractThe recent identification of three broadly neutralizing antibodies (bnAbs) against gp120-gp41 interface epitopes has expanded the targetable surface on the HIV-1 envelope glycoprotein (Env) trimer. ...The recent identification of three broadly neutralizing antibodies (bnAbs) against gp120-gp41 interface epitopes has expanded the targetable surface on the HIV-1 envelope glycoprotein (Env) trimer. By using biochemical, biophysical and computational methods, we map the previously unknown trimer epitopes of two related antibodies, 3BC315 and 3BC176. A cryo-EM reconstruction of a soluble Env trimer bound to 3BC315 Fab at 9.3 Å resolution reveals that the antibody binds between two gp41 protomers, and neutralizes the virus by accelerating trimer decay. In contrast, bnAb 35O22 binding to a partially overlapping quaternary epitope at the gp120-gp41 interface does not induce decay. A conserved gp41-proximal glycan at N88 was also shown to play a role in the binding kinetics of 3BC176 and 3BC315. Finally, our data suggest that the dynamic structure of the Env trimer influences exposure of bnAb epitopes.
External linksNat Commun / PubMed:26404402 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.887 - 9.3 Å
Structure data

EMDB-3067:
cryoEM reconstruction of 3BC315 Fab in complex with BG505 SOSIP.664 Env trimer
Method: EM (single particle) / Resolution: 9.3 Å

PDB-5awn:
Crystal structure of Human anti-HIV-1 broadly neutralizing antibody 3BC176 Fab
Method: X-RAY DIFFRACTION / Resolution: 1.887 Å

PDB-5cck:
Crystal structure of Human anti-HIV-1 broadly neutralizing antibody 3BC315 Fab
Method: X-RAY DIFFRACTION / Resolution: 1.95 Å

Chemicals

ChemComp-HOH:
WATER / Water

ChemComp-CXS:
3-CYCLOHEXYL-1-PROPYLSULFONIC ACID / pH buffer*YM / CAPS (buffer)

Source
  • Human Immunodeficiency Virus-1
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / HIV-1 / Env / broadly neutralizing antibody / bnAb / antibody

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