Location and chemical synthesis of a binding site for HIV-1 on the CD4 protein.
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.
D000911:Antibodies, Monoclonal / Q000276:immunology; D001667:Binding, Competitive; D002459:Cell Fusion; D004220:Disulfides / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006678:HIV / Q000276:immunology / Q000378:metabolism*; D015699:HIV Envelope Protein gp120; D006801:Humans; D007136:Immunoglobulins; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D011487:Protein Conformation; D011863:Radioimmunoassay; D015728:Receptors, HIV; D011991:Receptors, Virus / Q000276:immunology*; D012191:Retroviridae Proteins / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000382:microbiology*
D000911:Antibodies, Monoclonal; D004220:Disulfides; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D007136:Immunoglobulins; D010446:Peptide Fragments; D015728:Receptors, HIV; D011991:Receptors, Virus; D012191:Retroviridae Proteins