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

    Research output: Contribution to journalArticle

    627 Scopus citations

    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

    ASJC Scopus subject areas

    • General

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    Zhou, T., Xu, L., Dey, B., Hessell, A. J., Van Ryk, D., Xiang, S. H., Yang, X., Zhang, M. Y., Zwick, M. B., Arthos, J., Burton, D. R., Dimitrov, D. S., Sodroski, J., Wyatt, R., Nabel, G. J., & 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