Structural studies of the interleukin-19 subfamily of cytokines.
The interleukin-19 (IL-19) subfamily of cytokines is part of a larger family of homologs of IL-10 that includes two groups of proteins: five viral cytokines, and eight cellular cytokines, having quite different biological activities. Among proteins of the latter group, IL-19, IL-20, IL-22, and IL-24 were suggested to form a structurally unique IL-19 subfamily characterized by their structural features and aggregation state as monomers. IFN-lambda1, IFN-lambda2, and IFN-lambda3 are likely to belong to this subfamily, and it is still not clear whether IL-26 belongs to it or not. In spite of their differences in biological function, all cellular homologs of IL-10 used for signaling a set of five overlapping membrane-bound receptors: three long receptor chains (IL-20R1, IL-22R1, and IFN-lambdaR) and two short receptor chains (IL-20R2 and IL-10R2). Signal transduction is initiated when a cytokine binds two receptor chains, one long and one short, forming a ternary complex. Crystal structures of IL-19 and IL-22 showed that these cytokines consist of seven amphipathic helices of different length organized in helical bundle, covering an extensive hydrophobic core. Based on the similarity of the structures with the structure of a single domain of IL-10, and with the crystal structure of a binary IL-10/IL-10R1 complex, putative receptor binding sites on the surface of IL-19 and IL-22 were identified. This chapter summarizes the available structural data on the IL-19 subfamily of cytokines and their putative ligand/receptor complexes.
Zdanov
Alexander
A
Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
D016207:Cytokines / Q000737:chemistry*; D006801:Humans; D007378:Interleukins / Q000737:chemistry*; D011487:Protein Conformation; D018123:Receptors, Interleukin / Q000737:chemistry
D016207:Cytokines; C421250:IL19 protein, human; D007378:Interleukins; D018123:Receptors, Interleukin