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PMID: 9641677 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Nature ·Vol. 393 ·No. 6686 ·1998-06-18 ·Pages 648-59

Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA

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.

MeSH Terms
Amino Acid Sequence Animals CD4 Antigens/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
Chemicals
CD4 Antigens HIV Antibodies HIV Envelope Protein gp120 HIV Envelope Protein gp41 Immunoglobulin Fragments Receptors, CCR5
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kwong P D
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
Wyatt R
Robinson J
Sweet R W
Sodroski J
Hendrickson W A
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
0028-0836
DOI
10.1038/31405
Published
1998-06-18
Pages
648-59
Language
English
Region
England
NLM ID
0410462
PMCID
PMC5629912
Subset
IM
Grants
NIGMS NIH HHS · R01 GM034102 · United States
Databases
PDB
1GC1
Corrections
CommentIn
PMID: 9641673
External Links
PubMed source DOI: 10.1038/31405 PMC Full Text View journal details
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