Structural and Functional Attributes of the Interleukin-36 Receptor.

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.
Mesh Terms:
HEK293 Cells, Humans, Interleukin-1 Receptor Accessory Protein, Interleukin-18 Receptor alpha Subunit, Polymorphism, Genetic, Protein Domains, Signal Transduction, Structure-Activity Relationship
J Biol Chem
Date: Dec. 05, 2015
Download Curated Data For This Publication
234194
Switch View:
  • Interactions 2