Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01
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, 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
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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Source: PubMed