@article{0e84d02264df4c608eeffa74bdbf040a,
title = "Structural definition of a conserved neutralization epitope on HIV-1 gp120",
abstract = "The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 {\AA} resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1.",
author = "Tongqing Zhou and Ling Xu and Barna Dey and Hessell, {Ann J.} and {Van Ryk}, Donald and Xiang, {Shi Hua} and Xinzhen Yang and Zhang, {Mei Yun} and Zwick, {Michael B.} and James Arthos and Burton, {Dennis R.} and Dimitrov, {Dimiter S.} and Joseph Sodroski and Richard Wyatt and Nabel, {Gary J.} and Kwong, {Peter D.}",
note = "Funding Information: Acknowledgements We thank B. Graham, D. Hamer, S. Harrison, R. Pantophlet, W. Schief, L. Shapiro, I. Wilson and members of the Structural Biology Section, VRC, for discussions and comments on the manuscript; M. Gao for assistance with PDB deposit; H. Katinger for antibody 2G12; G. Lin for suggesting the use of swainsonine; S. Majeed for preparation of Fab 17b; J. Nelson for assistance with b12 ELISAs; M. Posner for antibody F105; J. Robinson for antibodies 17b, 1.5e and F91; J. Stuckey for assistance with figures; M. Venturi for assistance with gp120 production methodology; and the NIH AIDS Research and Reference Reagent Program for CD4. Support for this work was provided by the Intramural Research Program of the NIH, by the International AIDS Vaccine Initiative, by a grant from the Bill and Melinda Gates Foundation Grand Challenges in Global Heath Initiative, and by grants from the NIH. Use of SER-CAT at the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science.",
year = "2007",
month = feb,
day = "15",
doi = "10.1038/nature05580",
language = "English (US)",
volume = "445",
pages = "732--737",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7129",
}