Structural definition of a conserved neutralization epitope on HIV-1 gp120
By T. Zhou, Ling Xu, B. Dey, A. Hessell, D. V. Van Ryk, S. Xiang, Xinzhen Yang, Mei-Yun Zhang, M. Zwick, J. Arthos and 6 more. Nature, 2007
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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.
View Paper: https://www.semanticscholar.org/paper/0bbe45a0bb8c2acd4d551fdb98f65d979cd04605
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Citations in the corpus
- HIV-1 antiretroviral drug therapy. (2012, background): “The gp120 structure is shown as an overlay of two structures (2NY2 and 3HI1) (Zhou et al. 2007; Chen et al. 2009).”
- Efalizumab binding to the LFA-1 αL I domain blocks ICAM-1 binding via steric hindrance (2009, background): “A similar recognition mode of the antibody–antigen interaction with exclusive reliance on the VH CDRs has been observed in some other antibody–antigen complexes (44, 45).”
- Human Immunodeficiency Virus Type 1 Elite Neutralizers: Individuals with Broad and Potent Neutralizing Activity Identified by Using a High-Throughput Neutralization Assay together with an Analytical Selection Algorithm (2009, background): “Distribution of neutralization sensitivities of early/chronic HIV-1 Env clones on panel 2 among HIV-1-infected individuals previously identified as having broad neutralizing activity on panel 1.”
- Crystal structure of a soluble cleaved HIV-1 envelope trimer (2013, background): “Various structures of components of gp120 and gp41, alone and in complex with different ligands, have been determined (1-10).”