Epitopes described in "Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody."

Article Authors:P D Kwong; R Wyatt; J Robinson; R W Sweet; J Sodroski; W A Hendrickson
Article Title:Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody.
Reference Detail
Reference ID:1090
Abstract:The entry of human immunodeficiency virus (HIV) into cells requires the sequential interaction of the viral exterior envelope glycoprotein, gp120, with the CD4 glycoprotein and a chemokine receptor on the cell surface. These interactions initiate a fusion of the viral and cellular membranes. Although gp120 can elicit virus-neutralizing antibodies, HIV eludes the immune system. We have solved the X-ray crystal structure at 2.5 A resolution of an HIV-1 gp120 core complexed with a two-domain fragment of human CD4 and an antigen-binding fragment of a neutralizing antibody that blocks chemokine-receptor binding. The structure reveals a cavity-laden CD4-gp120 interface, a conserved binding site for the chemokine receptor, evidence for a conformational change upon CD4 binding, the nature of a CD4-induced antibody epitope, and specific mechanisms for immune evasion. Our results provide a framework for understanding the complex biology of HIV entry into cells and should guide efforts to intervene.
Affiliations:Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
Reference Type:Literature
PubMed ID:9641677
Journal Volume:393
Article Pages:648-59
Journal ISSN:1476-4687
Article Chemical List:Antigens, CD4;HIV Antibodies;HIV Envelope Protein gp120;HIV Envelope Protein gp41;Immunoglobulin Fragments;Receptors, CCR5
Article MeSH List:Amino Acid Sequence; Animals; Antigens, CD4(chemistry; immunology; metabolism); CHO Cells; Cricetinae; Cricetulus; Crystallography, X-Ray; Glycosylation; HIV Antibodies(chemistry; immunology); HIV Envelope Protein gp120(chemistry; immunology; metabolism); HIV Envelope Protein gp41(metabolism); Humans; Immunoglobulin Fragments(chemistry; immunology); Membrane Fusion; Models, Molecular; Molecular Sequence Data; Neutralization Tests; Protein Conformation; Receptors, CCR5(metabolism)
Article Comments:9641673 Nature. 1998 Jun 18;393(6686):630-1
Curation Last Updated:2014-10-03 19:37:47