title: Molecular modeling of the interleukin-19 receptor complex. Novel aspects of receptor recognition in the interleukin-10 cytokine family.
abstract: The interleukin-10 (IL-10) cytokine family consists of several viral and human homologs that exhibit distinct receptor binding specificities. In the present study, the complex between interleukin-19 (IL-19) and its physiological receptor-the interleukin-20 receptor alpha-chain (IL-20R1)-was modeled. The most prominent feature of this complex is an extended binding interface formed by a long loop of IL-20R1 and a bulge region of IL-19. The two regions exhibit complementary charges and have no structural counterparts in the IL-10/IL-10R1 complex but show some resemblance to the complex between interferon-gamma (IFN-gamma) and its receptor. Sequence comparison of the three cytokines (IL-19, IL-20, IL-24) that bind the IL-20R1 reveals a considerable conservation of the length of the interacting loops. One residue suggested to play a key role in receptor binding specificity is a conserved glutamate. The binding interface of IL-20R1 is rich in aromatic residues while the interfaces of its cytokine ligands are mainly formed by more flexible aliphatic amino acids. This structural feature might play an important role for the specific recognition of a single receptor chain by three different cytokines. [Figure: see text]. Comparison of the ligand/receptor interfaces in theA IL-10/IL-10R1,B IL-19/IL-20R1 andC IFN-gamma/receptor complexes. The translucent Connolly surfaces of the receptor and the ligand are shown in yellow and white, respectively. The backbone of the receptor and ligand are highlighted by a red and blue/green tube, respectively. For clarity, only one domain of the intertwined dimes is shown for IL-10 and IFN-gamma. Arrows denote the location of helix B and the corresponding structural elements in IL-19 and IFN-gamma as well as the location of receptor loop L2. As evident fromB andC an extended interaction surface is created in the IL-19/IL-20R1 and IFN-gamma/receptor complexes by the interaction of this structural element with a long loop of the respective receptor.
authors.affiliation: Abteilung Bioinformatik, Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Fahrstr. 17, 91054, Erlangen, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Preimel
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sticht
mesh_terms: D000595:Amino Acid Sequence; D016753:Interleukin-10 / Q000737:chemistry / Q000145:classification; D007378:Interleukins / Q000737:chemistry* / Q000145:classification; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D018123:Receptors, Interleukin / Q000737:chemistry*; D017385:Sequence Homology
chemical_list: C421250:IL19 protein, human; D007378:Interleukins; D018123:Receptors, Interleukin; C492510:interleukin-20 receptor; D016753:Interleukin-10