Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Science (Impact Factor: 31.48). 08/2010; 329(5993):811-7. DOI: 10.1126/science.1192819
Source: PubMed

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.


Available from: Tongqing Zhou, Jun 12, 2015
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