Structure-function relationships for the IL 2-receptor system. II. Localization of an IL 2 binding site on high and low affinity receptors.
The ligand-binding component of high and low affinity IL 2 receptors is a 55,000 m.w. glycoprotein termed Tac. Correlating the structure and function of this molecule should provide insight into the mechanism of IL 2-initiated signal transduction and the structural basis for high and low affinity receptor forms. As a first step in this process, various approaches were used to localize the IL 2 binding region of the Tac molecule. Antibodies prepared to synthetic fragments of Tac were tested for their ability to interfere with IL 2 binding and bioactivity. The results delineated segments in the C-terminal portion of the molecule which appeared to be distal to the ligand binding site. In a more direct approach, radioiodinated IL 2 was cross-linked to high and low affinity receptors, and the resulting complexes were subjected to mild tryptic digestion. Consistent with the antibody data, the IL 2 remained covalently associated with an N-terminal tryptic fragment which apparently consisted of residues 1-83 of the Tac protein. These results suggest that the N-terminal region of the Tac molecule contains important contact sites for ligand-receptor interaction.
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis* / Q000276:immunology; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D010455:Peptides / Q000032:analysis; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000032:analysis* / Q000276:immunology; D015375:Receptors, Interleukin-2; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000032:analysis*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000906:Antibodies; D000954:Antigens, Surface; D000939:Epitopes; D007376:Interleukin-2; D010455:Peptides; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7