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, Peter D. Kwong

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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

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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. J., 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 J.; 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, AJ, Van Ryk, D, Xiang, S-H, 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 T, Xu L, Dey B, Hessell AJ, Van Ryk D, Xiang S-H et al. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature. 2007 Feb 15;445(7129):732-737. https://doi.org/10.1038/nature05580
Zhou, Tongqing ; Xu, Ling ; Dey, Barna ; Hessell, Ann J. ; 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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