Structural definition of a conserved neutralization epitope on HIV-1 gp120

Tongqing Zhou, Ling Xu, Barna Dey, Ann J. Hessell, Donald Van Ryk, Shi-Hua Xiang, Xinzhen Yang, Mei-Yun Zhang, Michael B. Zwick, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Joseph Sodroski, Richard Wyatt, Gary J. Nabel and Peter D. Kwong ()
Additional contact information
Tongqing Zhou: Vaccine Research Center, and,
Ling Xu: Vaccine Research Center, and,
Barna Dey: Vaccine Research Center, and,
Ann J. Hessell: Scripps Research Institute, La Jolla, California 92037, USA
Donald Van Ryk: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Shi-Hua Xiang: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Xinzhen Yang: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Mei-Yun Zhang: Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA
Michael B. Zwick: Scripps Research Institute, La Jolla, California 92037, USA
James Arthos: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Dennis R. Burton: Scripps Research Institute, La Jolla, California 92037, USA
Dimiter S. Dimitrov: Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA
Joseph Sodroski: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Richard Wyatt: Vaccine Research Center, and,
Gary J. Nabel: Vaccine Research Center, and,
Peter D. Kwong: Vaccine Research Center, and,

Nature, 2007, vol. 445, issue 7129, 732-737

Abstract: Abstract The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 Å resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.

Date: 2007
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/nature05580 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:445:y:2007:i:7129:d:10.1038_nature05580

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature05580

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().