Characterization of the interaction between interleukin-13 and interleukin-13 receptors.
Interleukin-13 (IL-13) possesses two types of receptor: the heterodimer, composed of the IL-13Ralpha1 chain (IL-13Ralpha1) and the IL-4Ralpha chain (IL-4Ralpha), transducing the IL-13 signals; and the IL-13Ralpha2 chain (IL-13Ralpha2), acting as a nonsignaling "decoy" receptor. Extracellular portions of both IL-13Ralpha1 and IL-13Ralpha2 are composed of three fibronectin type III domains, D1, D2, and D3, of which the last two comprise the cytokine receptor homology modules (CRHs), a common structure of the class I cytokine receptor superfamily. Thus far, there has been no information about the critical amino acids of the CRHs or the role of the D1 domains of IL-13Ralpha1 and IL-13Ralpha2 in binding to IL-13. In this study, we first built the homology modeling of the IL-13.hIL-13 receptor complexes and then predicted the amino acids involved in binding to IL-13. By incorporating mutations into these amino acids, we identified Tyr-207, Asp-271, Tyr-315, and Asp-318 in the CRH of human IL-13Ralpha2, and Leu-319 and Tyr-321 in the CRH of human IL-13Ralpha1, as critical residues for binding to IL-13. Tyr-315 in IL-13Ralpha2 and Leu-319 in IL-13Ralpha1 are positionally conserved hydrophobic amino acid residues. Furthermore, by using D1 domain-deleted mutants, we found that the D1 domain is needed for the expression of IL-13Ralpha2, but not IL-13Ralpha1, and that the D1 domain of IL-13Ralpha1 is important for binding to IL-13, but not to IL-4. These results provide the basis for a precise understanding of the interaction between IL-13 and its receptors.
Arima
Kazuhiko
K
Division of Medical Biochemistry, Department of Biomolecular Sciences, Center for Comprehensive Community Medicine, Saga Medical School, Saga 849-8501, Japan.
Sato
Kazuo
K
Tanaka
Go
G
Kanaji
Sachiko
S
Terada
Tohru
T
Honjo
Eijiro
E
Kuroki
Ryota
R
Matsuo
Yo
Y
Izuhara
Kenji
K
D000595:Amino Acid Sequence; D001665:Binding Sites; D016207:Cytokines / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000737:chemistry; D017353:Gene Deletion; D006801:Humans; D018793:Interleukin-13 / Q000737:chemistry*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000378:metabolism; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018123:Receptors, Interleukin / Q000737:chemistry*; D053660:Receptors, Interleukin-13; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D016207:Cytokines; D005353:Fibronectins; C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D011994:Recombinant Proteins; D015847:Interleukin-4; D008156:Luciferases