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| Article Authors: | 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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| Article Title: | Structural definition of a conserved neutralization epitope on HIV-1 gp120. |
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| Reference ID: | 1022128 |
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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 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. |
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| Affiliations: | Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. |
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| Date: | 2007 |
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| Reference Type: | Literature |
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| PubMed ID: | 17301785 |
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| Journal: | Nature |
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| Journal Volume: | 445 |
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| Article Pages: | 732-7 |
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| Journal ISSN: | 1476-4687 |
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| Article Chemical List: | Antigens, CD4;Epitopes;HIV Antibodies;HIV Envelope Protein gp120 |
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| Article MeSH List: | Antigens, CD4(chemistry; metabolism); Binding Sites; Conserved Sequence; Epitopes(chemistry; immunology); HIV Antibodies(immunology; pharmacology); HIV Envelope Protein gp120(chemistry; immunology; metabolism); HIV-1(chemistry; drug effects; immunology; physiology); Models, Molecular; Molecular Weight; Neutralization Tests; Protein Conformation |
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| Curation Last Updated: | 2013-05-28 22:27:18 |
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