Download MendeleyStructural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120.
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., Mascola, J.R., Kwong, P.D.(2009) Science 326: 1123-1127
- PubMed: 19965434
- DOI: https://doi.org/10.1126/science.1175868
- Primary Citation of Related Structures:
3HI1, 3IDX, 3IDY - PubMed 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.
Organizational Affiliation:
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
