title: Definition and spatial location of mouse interleukin-2 residues that interact with its heterotrimeric receptor.
abstract: The high affinity receptor for interleukin-2 (IL-2) contains three subunits called IL-2R alpha, beta and gamma. A biological and receptor binding analysis based on 1393 different mutant mouse IL-2 (mIL-2) proteins was used to define the function of each of the 149 residues. By this genetic analysis, 44 residues were assigned important functions, 21 of which were structural. The remaining 23 residues consisted of 19 residues, from three separate regions, that were important for IL-2R alpha interaction; three residues, from two separate regions, that were important for IL-2R beta interaction; and a single residue important for IL-2R gamma interaction. We built a model mIL-2 structure based on the homologous human IL-2 (hIL-2) crystal structure. The roles of the 21 residues presumed to be important for structure were consistent with the model. Despite discontinuity in the primary sequence, the residues specific for each IL-2R subunit interaction were clustered and located to three disparate regions of the tertiary mIL-2 structure. The relative spatial locations of these three surfaces are different from the two receptor binding sites known for the structurally related human growth hormone and the significance of this observation is discussed.
authors.affiliation: DNAX Research Institute for Molecular and Cellular Biology, Palo Alto, CA 94304-1104.
authors.forename: S M
authors.initials: SM
authors.lastname: Zurawski
authors.forename: F
authors.initials: F
authors.lastname: Vega
authors.forename: E L
authors.initials: EL
authors.lastname: Doyle
authors.forename: B
authors.initials: B
authors.lastname: Huyghe
authors.forename: K
authors.initials: K
authors.lastname: Flaherty
authors.forename: D B
authors.initials: DB
authors.lastname: McKay
authors.forename: G
authors.initials: G
authors.lastname: Zurawski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D007376:Interleukin-2 / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015375:Receptors, Interleukin-2 / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2