Identification of three adjacent amino acids of interleukin-2 receptor beta chain which control the affinity and the specificity of the interaction with interleukin-2.
The beta chain of the interleukin-2 (IL-2) receptor (IL-2R beta) and the interleukin-3 (IL-3) binding protein AIC2A are members of the family of cytokine receptors, which also includes the receptors for growth hormone (GHR) and prolactin. A four amino acid sequence of AIC2A has recently been shown to be critical for IL-3 binding. We analyze here the function of the analogous sequence of human IL-2R beta and identify three amino acids, Ser132, His133 and Tyr134, which play a critical role in IL-2 binding. We show that some mutant IL-2 proteins with substitutions of a critical Asp residue in the N-terminal alpha-helix bind the mutant IL-2R beta receptor with a higher affinity than the wild-type receptor. This suggests that the critical Asp34 in the ligand and the sequence Ser-His-Tyr (positions 132-134) in the receptor interact directly. On the double barrel beta-stranded structural model of cytokine receptors, the residues important for ligand binding in IL-2R beta, AIC2A and GHR map to strikingly similar locations within a barrel, with the interesting difference that it is the N-terminal barrel for GHR and the C-terminal barrel for IL-2R beta and AIC2A.
Imler
J L
JL
Department of Molecular Biology, DNAX Research Institute, Palo Alto, CA 94304.
Miyajima
A
A
Zurawski
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D015375:Receptors, Interleukin-2 / Q000235:genetics* / Q000378:metabolism*; D016185:Receptors, Interleukin-3; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D002352:Carrier Proteins; D007376:Interleukin-2; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2; D016185:Receptors, Interleukin-3; C072185:Csf2rb2 protein, mouse