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Structural and functional attributes of the interleukin-36 receptor
G. Yi, J.A. Ybe, , G. Caviness, E. Raymond, R. Ganesan, M.L. Mbow, C.C. Kao
Published in American Society for Biochemistry and Molecular Biology Inc.
PMID: 27307043
Volume: 291
Issue: 32
Pages: 16597 - 16609
Signal transduction by the IL-36 receptor (IL-36R) is linked to several human diseases. However, the structure and function of the IL-36R is not well understood. A molecular model of the IL-36R complex was generated and a cell-based reporter assay was established to assess the signal transduction of recombinant subunits of the IL-36R. Mutational analyses and functional assays have identified residues of the receptor subunit IL-1Rrp2 needed for cytokine recognition, stable protein expression, disulfide bond formation and glycosylation that are critical for signal transduction. We also observed that, overexpression of ectodomain (ECD) of Il-1Rrp2 or IL-1RAcP exhibited dominant-negative effect on IL-36R signaling. The presence of IL-36 cytokine significantly increased the interaction of IL-1Rrp2 ECD with the co-receptor IL-1RAcP. Finally, we found that single nucleotide polymorphism A471T in the Toll-interleukin 1 receptor domain (TIR) of the IL-1Rrp2 that is present in ∼2% of the human population, down-regulated IL-36R signaling by a decrease of interaction with IL-1RAcP. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
About the journal
JournalJournal of Biological Chemistry
PublisherAmerican Society for Biochemistry and Molecular Biology Inc.