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

Tongqing Zhou, Ling Xu, Barna Dey, Ann 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, Peter D. Kwong

Research output: Contribution to journalArticle

613 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)732-737
Number of pages6
JournalNature
Volume445
Issue number7129
DOIs
StatePublished - Feb 15 2007
Externally publishedYes

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HIV-1
Epitopes
CD4 Antigens
Antibodies
Antibody Binding Sites
Neutralizing Antibodies
Glycosylation
Glycoproteins
Binding Sites

ASJC Scopus subject areas

  • General

Cite this

Zhou, T., Xu, L., Dey, B., Hessell, A., Van Ryk, D., Xiang, S. H., ... Kwong, P. D. (2007). Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature, 445(7129), 732-737. https://doi.org/10.1038/nature05580

Structural definition of a conserved neutralization epitope on HIV-1 gp120. / Zhou, Tongqing; Xu, Ling; Dey, Barna; Hessell, Ann; Van Ryk, Donald; Xiang, Shi Hua; Yang, Xinzhen; Zhang, Mei Yun; Zwick, Michael B.; Arthos, James; Burton, Dennis R.; Dimitrov, Dimiter S.; Sodroski, Joseph; Wyatt, Richard; Nabel, Gary J.; Kwong, Peter D.

In: Nature, Vol. 445, No. 7129, 15.02.2007, p. 732-737.

Research output: Contribution to journalArticle

Zhou, T, Xu, L, Dey, B, Hessell, A, Van Ryk, D, Xiang, SH, Yang, X, Zhang, MY, Zwick, MB, Arthos, J, Burton, DR, Dimitrov, DS, Sodroski, J, Wyatt, R, Nabel, GJ & Kwong, PD 2007, 'Structural definition of a conserved neutralization epitope on HIV-1 gp120', Nature, vol. 445, no. 7129, pp. 732-737. https://doi.org/10.1038/nature05580
Zhou, Tongqing ; Xu, Ling ; Dey, Barna ; Hessell, Ann ; Van Ryk, Donald ; Xiang, Shi Hua ; Yang, Xinzhen ; Zhang, Mei Yun ; Zwick, Michael B. ; Arthos, James ; Burton, Dennis R. ; Dimitrov, Dimiter S. ; Sodroski, Joseph ; Wyatt, Richard ; Nabel, Gary J. ; Kwong, Peter D. / Structural definition of a conserved neutralization epitope on HIV-1 gp120. In: Nature. 2007 ; Vol. 445, No. 7129. pp. 732-737.
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