Structural features of the interleukin-10 family of cytokines.
The interleukin-10 (IL-10) family of cytokines includes IL-10, a number of its viral gene homologs, and eight recently discovered cellular cytokines (IL-19, IL-20, IL-22, IL-24, IL-26, IFN-lambda1, IFN-lambda2, IFN-lambda3). IL-10 is an intercalated dimer consisting of two six-helix bundle domains. Signal transduction occurs when each domain of IL-10 binds to two receptor chains, IL-10R1 and IL-10R2. Viral homologs use the same IL-10 receptor system, while cellular homologs use their own receptors: three long receptor chains (IL-20R1, IL-22R1 and IFN-lambda1R1) and two short receptor chains (IL-20R2 and IL-10R2). Most of the cellular homologs belong to the IL-19 subfamily of cytokines including IL-19, IL-20, IL-22 and IL-24. It is likely that IFN-lambda1, IFN-lambda2, and IFN-lambda3 also belong to the same subfamily. All these proteins are monomers in solution. Crystal structures of IL-19 and IL-22 show that the molecules consist of seven helices (A-G) forming a seven-helix bundle with compact hydrophobic core inside. Structures of complexes of IL-10 and CMVIL-10 with an extracellular domain of high affinity receptor IL-10R1 (sIL-10R1) showed that ligand/receptor interactions are of mostly polar nature, with two hydrophobic patches around receptor residues Tyr43 and Phe143 at the top and bottom of the interface. The location and structure of the binding site for the second receptor chain are still unknown. It has also been shown that in the case of IL-19 and IL-20, IL-20R2 rather than IL-20R1 is a high-affinity receptor chain. This review summarizes all published three-dimensional structures of the cytokines representing the IL-10 family of homologs, including the IL-19 subfamily and their interaction with appropriate receptors.
Zdanov
Alexander
A
Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA. zdanov@ncifcrf.gov
D016207:Cytokines / Q000737:chemistry / Q000145:classification*; D006801:Humans; D016753:Interleukin-10 / Q000737:chemistry / Q000145:classification*; D008958:Models, Molecular; D011487:Protein Conformation
D016207:Cytokines; D016753:Interleukin-10