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Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike.
Lee, Jeong Hyun; Leaman, Daniel P; Kim, Arthur S; Torrents de la Peña, Alba; Sliepen, Kwinten; Yasmeen, Anila; Derking, Ronald; Ramos, Alejandra; de Taeye, Steven W; Ozorowski, Gabriel; Klein, Florian; Burton, Dennis R; Nussenzweig, Michel C; Poignard, Pascal; Moore, John P; Klasse, Per Johan; Sanders, Rogier W; Zwick, Michael B; Wilson, Ian A; Ward, Andrew B.
Affiliation
  • Lee JH; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
  • Leaman DP; International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla California 92037, USA.
  • Kim AS; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.
  • Torrents de la Peña A; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA.
  • Sliepen K; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA.
  • Yasmeen A; Department of Medicinal Microbiology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
  • Derking R; Department of Medicinal Microbiology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
  • Ramos A; Weill Medical College of Cornell University, New York, New York 10065, USA.
  • de Taeye SW; Department of Medicinal Microbiology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
  • Ozorowski G; International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla California 92037, USA.
  • Klein F; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA.
  • Burton DR; Department of Medicinal Microbiology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
  • Nussenzweig MC; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
  • Poignard P; International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla California 92037, USA.
  • Moore JP; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA.
  • Klasse PJ; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
  • Sanders RW; International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla California 92037, USA.
  • Zwick MB; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA.
  • Wilson IA; Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts 02114, USA.
  • Ward AB; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
Nat Commun ; 6: 8167, 2015 Sep 25.
Article in En | MEDLINE | ID: mdl-26404402
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Antibodies / HIV Envelope Protein gp41 / HIV Envelope Protein gp120 / HIV-1 / Antibodies, Neutralizing Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2015 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Antibodies / HIV Envelope Protein gp41 / HIV Envelope Protein gp120 / HIV-1 / Antibodies, Neutralizing Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2015 Document type: Article Affiliation country: