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

Article

关键词: IMMUNODEFICIENCY-VIRUS TYPE-1;    ENVELOPE GLYCOPROTEIN;    MONOCLONAL-ANTIBODIES;    RECEPTOR;    RECOGNITION;    ANTIGEN;    PROTEIN;    DOMAIN;    IDENTIFICATION;    REGIONS;   

DOI  :  10.1038/nature05580

来源: SCIE

【 摘 要 】

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 angstrom 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.

【 授权许可】

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