Location and Chemical Synthesis of a Binding Site for HIV-1 on the CD4 Protein

• Published in: Science (American Association for the Advancement of Science) Vol. 240; no. 4857; pp. 1335 - 1339
• Main Authors: Jameson, Bradford A., Rao, Patricia E., Kong, Lilly I., Hahn, Beatrice H., Shaw, George M., Hood, Leroy E., Stephen B. H. Kent
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 03.06.1988; American Association for the Advancement of Science
• Subjects: AIDS; AIDS/HIV; Antibodies; Antibodies, Monoclonal - immunology; Binding, Competitive; Biological and medical sciences; Cell Fusion; Cell receptors; Disulfides; Disulfides - metabolism; DNA probes; Epitopes; Epitopes - immunology; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; HIV; HIV (Viruses); HIV - immunology; HIV - metabolism; HIV 1; HIV Envelope Protein gp120; human immunodeficiency virus 1; Humans; Immunoglobulins; Messenger RNA; Microbiology; Molecular structure; Neurons; Peptide Fragments - chemical synthesis; Peptide Fragments - immunology; Protein Conformation; Protein research; Pyramidal cells; Radioimmunoassay; Receptors, HIV; Receptors, Virus - immunology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Retroviridae Proteins - immunology; T lymphocytes; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - microbiology; Virology; Virus; Site specificity; HIV-1 virus; Chemical bond; Retroviridae; Molecular interaction; Human immunodeficiency virus; Localization; Lymphocyte
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2453925

The human immunodeficiency virus type 1 (HIV-1) uses the CD4 protein as a receptor for infection of susceptible cells. A candidate structure for the HIV-1 binding site on the CD4 protein was identified by epitope mapping with a family of eight functionally distinct CD4-specific monoclonal antibodies in conjunction with a panel of large CD4-derived synthetic peptides. All of the seven epitopes that were located reside within two immunoglobulin-like disulfide loops situated between residues 1 and 168 of the CD4 protein. The CD4-specific monoclonal antibody OKT4A, a potent inhibitor of HIV-1 binding, recognized a site between residues 32 and 47 on the CD4 protein. By analogy to other members of the immunoglobulin superfamily of proteins, this particular region has been predicted to exist as a protruding loop. A synthetic analog of this loop (residues 25 to 58) showed a concentration-dependent inhibition of HIV-1--induced cell fusion. It is proposed that a loop extending from residues 37 to 53 of the CD4 protein is a binding site for the AIDS virus.