Epitopes described in "Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01."

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
Article Title:Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01.
Reference Detail
Reference ID:1022153
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.
Affiliations:Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Reference Type:Literature
PubMed ID:20616231
Journal Volume:329
Article Pages:811-7
Journal ISSN:1095-9203
Article Chemical List:AIDS Vaccines;Antibodies, Neutralizing;Antigens, CD4;Epitopes;HIV Antibodies;HIV Envelope Protein gp120;Immunoglobulin Fab Fragments;gp120 protein, Human immunodeficiency virus 1
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; genetics; immunology); HIV-1(immunology); Humans; Immunoglobulin Fab Fragments(chemistry; immunology; metabolism); Models, Molecular; Molecular Mimicry; Molecular Sequence Data; Neutralization Tests; Protein Conformation; Protein Structure, Tertiary
Curation Last Updated:2015-06-05 02:45:24