Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120

Lei Chen, Young Do Kwon, Tongqing Zhou, Xueling Wu, Sijy O'Dell, Lisa Cavacini, Ann J. Hessell, Marie Pancera, Min Tang, Ling Xu, Zhi Yong Yang, Mei Yun Zhang, James Arthos, Dennis R. Burton, Dimiter S. Dimitrov, Gary J. Nabel, Marshall R. Posner, Joseph Sodroski, Richard Wyatt, John R. MascolaPeter D. Kwong

Research output: Contribution to journalArticle

Abstract

The site on HIV-1 gp120 that binds to the CD4 receptor is vulnerable to antibodies. However, most antibodies that interact with this site cannot neutralize HIV-1. To understand the basis of this resistance, we determined co-crystal structures for two poorly neutralizing, CD4-binding site (CD4BS) antibodies, F105 and b13, in complexes with gp120. Both antibodies exhibited approach angles to gp120 similar to those of CD4 and a rare, broadly neutralizing CD4BS antibody, b12. Slight differences in recognition, however, resulted in substantial differences in F105- and b13-bound conformations relative to b12-bound gp120. Modeling and binding experiments revealed these conformations to be poorly compatible with the viral spike. This incompatibility, the consequence of slight differences in CD4BS recognition, renders HIV-1 resistant to all but the most accurately targeted antibodies.

Original languageEnglish (US)
Pages (from-to)1123-1127
Number of pages5
JournalScience
Volume326
Issue number5956
DOIs
StatePublished - Nov 20 2009
Externally publishedYes

ASJC Scopus subject areas

  • General

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    Chen, L., Do Kwon, Y., Zhou, T., Wu, X., O'Dell, S., Cavacini, L., Hessell, A. J., Pancera, M., Tang, M., Xu, L., Yang, Z. Y., Zhang, M. Y., Arthos, J., Burton, D. R., Dimitrov, D. S., Nabel, G. J., Posner, M. R., Sodroski, J., Wyatt, R., ... Kwong, P. D. (2009). Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120. Science, 326(5956), 1123-1127. https://doi.org/10.1126/science.1175868