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| Article Authors: | Tongqing Zhou; Ivelin Georgiev; Xueling Wu; Zhi-Yong Yang; Kaifan Dai; Andrés Finzi; Young Do Kwon; Johannes F Scheid; Wei Shi; Ling Xu; Yongping Yang; Jiang Zhu; Michel C Nussenzweig; Joseph Sodroski; Lawrence Shapiro; Gary J Nabel; John R Mascola; Peter D Kwong |
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| Article Title: | Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. |
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| Reference ID: | 1022153 |
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| Abstract: | During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies. |
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| Affiliations: | Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA. |
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| Date: | 2010 |
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| Reference Type: | Literature |
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| PubMed ID: | 20616231 |
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| Journal: | Science |
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| Journal Volume: | 329 |
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| Article Pages: | 811-7 |
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| Journal ISSN: | 1095-9203 |
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| Article Chemical List: | AIDS Vaccines;Antibodies, Neutralizing;Antigens, CD4;Binding Sites, Antibody;Epitopes;HIV Antibodies;HIV Envelope Protein gp120;Immunoglobulin Fab Fragments |
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| Article MeSH List: | AIDS Vaccines; Amino Acid Sequence; Antibodies, Neutralizing(chemistry; immunology); Antibody Affinity; Antigenic Variation; Antigens, CD4(chemistry; immunology; metabolism); Base Sequence; Binding Sites, Antibody; Crystallography, X-Ray; Epitopes(immunology); HIV Antibodies(chemistry; immunology); HIV Envelope Protein gp120(chemistry; immunology; metabolism); HIV-1(immunology); Humans; Immunoglobulin Fab Fragments(chemistry; immunology; metabolism); Models, Molecular; Molecular Mimicry; Molecular Sequence Data; Neutralization Tests; Protein Conformation; Protein Structure, Tertiary |
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| Curation Last Updated: | 2013-05-28 22:27:49 |
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