Membrane-Bound Receptors of the Interleukin-10 Family of Cytokines

Author(s): Alexander Zdanov.

Journal Name:Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Volume 5 , Issue 3 , 2006

Abstract:

The interleukin-10 (IL-10) family of cytokines includes IL-10, its viral homologs, and eight cellular cytokines: IL-19, IL-20, IL-22, IL-24, IL-26, IFN-λ1, IFN-λ2, and IFN-λ3. Cellular homologs use for signaling five recently discovered membrane-bound receptors: three long receptor chains (IL-20R1, IL-22R1, and IFN-λR) and two short receptor chains (IL-20R2 and IL-10R2). Signal transduction is initiated when cytokine binds two receptor chains, one long and one short, forming a ternary complex. Based on the analysis of known structures of ternary and binary complexes, a homology model of the structure of the ternary complex of IL-10/sIL-10R1/sIL-10R2 has been generated. The structure agrees well with all published experimental data, including the crystal structure of the binary IL-10/sIL-10R1 complex and data of peptide scans, mapping the sIL-10R2 binding site. sIL-10R1, sIL-10R2, and inter-receptor interface sites show that most of the intermolecular interactions have a polar nature, although hydrophobic interactions constituting between 20% and 35% from the total number of interactions are also important. Putative complexes of other cytokines of the IL-10 family and the role of glycosylation in ligand/receptor interactions and how it affects biological activity are also discussed.

Keywords: Cytokines, interleukin-10, receptor, signal transduction, family of cytokines, ligand/receptor interactions, fibronectin type III domain

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Article Details

VOLUME: 5
ISSUE: 3
Year: 2006
Page: [207 - 214]
Pages: 8
DOI: 10.2174/187152306778017728
Price: $58