期刊
SCIENCE
卷 329, 期 5993, 页码 811-817出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1192819
关键词
-
资金
- NIH
- International AIDS Vaccine Initiative's Neutralizing Antibody Consortium
- U.S. Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]
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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