title: Recombinant interleukin-2 analogs. Dynamic probes for receptor structure.
abstract: Interleukin-2 (IL-2) and its receptor complex have become one of the most studied members of a growing family of protein hormones characterized by structural similarities in both ligands and their receptors. Structure-function studies of IL-2 have been complicated by the multimeric nature of its receptor. Two receptor subunits (55- and 75-kDa type I cell surface proteins) can participate to form the high affinity binding site. Although the IL-2 is apparently unique in some respects, similar subunit cooperativity has now been shown to be a common feature for other members of this receptor family. The availability of cell lines expressing the individual IL-2 receptor subunits has allowed detailed analysis of subunit binding characteristics. Results regarding the relationship of molecular recognition at each subunit to the mechanism of ligand binding at the high affinity site, however, have led to different interpretations. In this study we have employed previously prepared C-terminal IL-2 mutant proteins to examine receptor binding at all three classes using a variety of equilibrium and kinetic techniques. These results indicate that the high affinity IL-2 receptor complex includes the p55/p75 heterodimer prior to IL-2 binding and that both receptor subunits participate simultaneously in ligand capture.
authors.affiliation: CytoMed Inc., Cambridge, Massachusetts 02139.
authors.forename: B E
authors.initials: BE
authors.lastname: Landgraf
authors.forename: B
authors.initials: B
authors.lastname: Goldstein
authors.forename: D P
authors.initials: DP
authors.lastname: Williams
authors.forename: J R
authors.initials: JR
authors.lastname: Murphy
authors.forename: T R
authors.initials: TR
authors.lastname: Sana
authors.forename: K A
authors.initials: KA
authors.lastname: Smith
authors.forename: T L
authors.initials: TL
authors.lastname: Ciardelli
mesh_terms: D001667:Binding, Competitive; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D016254:Mutagenesis, Insertional; D011487:Protein Conformation; D015375:Receptors, Interleukin-2 / Q000737:chemistry*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins