Epitopes described in "Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120."

Article Authors: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 Mascola; Peter D Kwong
Article Title:Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120.
Reference Detail
Reference ID:1022139
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.
Affiliations:Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Reference Type:Literature
PubMed ID:19965434
Journal Volume:326
Article Pages:1123-7
Journal ISSN:1095-9203
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@86a7996;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@6546b2b;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@1047d74c;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@5c87c6ed;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@56152110;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@52dcd97;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@2147729;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@d9b25d0
Article MeSH List:Amino Acid Sequence; Antibodies, Neutralizing(chemistry; immunology; metabolism); Antigens, CD4(chemistry; metabolism); Binding Sites; Binding Sites, Antibody; Crystallography, X-Ray; Epitopes; HIV Antibodies(chemistry; immunology; metabolism); HIV Envelope Protein gp120(chemistry; immunology; metabolism); HIV-1; Humans; Hydrophobic and Hydrophilic Interactions; Immune Evasion; Models, Molecular; Molecular Sequence Data; Peptide Fragments(chemistry; immunology; metabolism); Protein Conformation
Curation Last Updated:2015-01-17 23:32:33