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| Article Authors: | Lei Chen; Young Do Kwon; Tongqing Zhou; Xueling Wu; Sijy O'Dell; Lisa Cavacini; Ann J Hessell; Marie Pancera; Min Tang; Ling Xu; Zhi-Yong Yang; Mei-Yun Zhang; James Arthos; Dennis R Burton; Dimiter S Dimitrov; Gary J Nabel; Marshall R Posner; Joseph Sodroski; Richard Wyatt; John R Mascola; Peter D Kwong |
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| Article Title: | Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120. |
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| Reference ID: | 1022139 |
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| Abstract: | The site on HIV-1 gp120 that binds to the CD4 receptor is vulnerable to antibodies. However, most antibodies that interact with this site cannot neutralize HIV-1. To understand the basis of this resistance, we determined co-crystal structures for two poorly neutralizing, CD4-binding site (CD4BS) antibodies, F105 and b13, in complexes with gp120. Both antibodies exhibited approach angles to gp120 similar to those of CD4 and a rare, broadly neutralizing CD4BS antibody, b12. Slight differences in recognition, however, resulted in substantial differences in F105- and b13-bound conformations relative to b12-bound gp120. Modeling and binding experiments revealed these conformations to be poorly compatible with the viral spike. This incompatibility, the consequence of slight differences in CD4BS recognition, renders HIV-1 resistant to all but the most accurately targeted antibodies. |
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| Affiliations: | Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. |
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| Date: | 2009 |
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| Reference Type: | Literature |
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| PubMed ID: | 19965434 |
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| Journal: | Science |
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| Journal Volume: | 326 |
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| Article Pages: | 1123-7 |
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| Journal ISSN: | 1095-9203 |
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| Article Chemical List: | Antibodies, Neutralizing;Antigens, CD4;Binding Sites, Antibody;Epitopes;HIV Antibodies;HIV Envelope Protein gp120;HIV envelope protein gp120 (305-321);Peptide Fragments;gp120 protein, Human immunodeficiency virus 1 |
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| Article MeSH List: | Amino Acid Sequence; Antibodies, Neutralizing(chemistry; immunology; metabolism); Antigens, CD4(chemistry; metabolism); Binding Sites; Binding Sites, Antibody; Crystallography, X-Ray; Epitopes; HIV Antibodies(chemistry; immunology; metabolism); HIV Envelope Protein gp120(chemistry; immunology; metabolism); HIV-1; Humans; Hydrophobic and Hydrophilic Interactions; Immune Evasion; Models, Molecular; Molecular Sequence Data; Peptide Fragments(chemistry; immunology; metabolism); Protein Conformation |
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| Curation Last Updated: | 2013-05-28 22:27:21 |
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