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|2ny1, resolution 1.99Å ()|
|Gene:||CD4 (Homo sapiens)|
|Related:||1gc1, 1rzj, 1rzk, 2nxy, 2nxz, 2ny0, 2ny2, 2ny3, 2ny4, 2ny5, 2ny6, 2ny7|
HIV-1 gp120 Envelope Glycoprotein (I109C, T257S, S334A, S375W, Q428C) Complexed with CD4 and Antibody 17b
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 A 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.
Structural definition of a conserved neutralization epitope on HIV-1 gp120., Zhou T, Xu L, Dey B, Hessell AJ, 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, Nature. 2007 Feb 15;445(7129):732-7. PMID:17301785
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Zhou T, Xu L, Dey B, Hessell AJ, 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. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature. 2007 Feb 15;445(7129):732-7. PMID:17301785 doi:http://dx.doi.org/10.1038/nature05580