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.
Figures
![Figure 1. Structure of antibody VRC01 in…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2981354/bin/nihms215672f1.jpg)
![Figure 2. Structural mimicry of CD4 interaction…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2981354/bin/nihms215672f2.jpg)
![Figure 3. Structural basis of antibody VRC01…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2981354/bin/nihms215672f3.jpg)
![Figure 4. Natural resistance to antibody VRC01](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2981354/bin/nihms215672f4.jpg)
![Figure 5. Unusual VRC01 features](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2981354/bin/nihms215672f5.jpg)
![Figure 6. Somatic maturation and VRC01 affinity](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2981354/bin/nihms215672f6.jpg)
Source: PubMed