PMID- 27307043 OWN - NLM STAT- MEDLINE DCOM- 20170505 LR - 20210205 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 291 IP - 32 DP - 2016 Aug 5 TI - Structural and Functional Attributes of the Interleukin-36 Receptor. PG - 16597-609 LID - 10.1074/jbc.M116.723064 [doi] AB - 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 approximately 2% of the human population, down-regulated IL-36R signaling by a decrease of interaction with IL-1RAcP. CI - (c) 2016 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Yi, Guanghui AU - Yi G AD - From the Departments of Molecular and Cellular Biochemistry and. FAU - Ybe, Joel A AU - Ybe JA AD - Environmental Health, School of Public Health, Indiana University, Bloomington, Indiana 47405 and. FAU - Saha, Siddhartha S AU - Saha SS AD - From the Departments of Molecular and Cellular Biochemistry and. FAU - Caviness, Gary AU - Caviness G AD - Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877. FAU - Raymond, Ernest AU - Raymond E AD - Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877. FAU - Ganesan, Rajkumar AU - Ganesan R AD - Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877. FAU - Mbow, M Lamine AU - Mbow ML AD - Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877. FAU - Kao, C Cheng AU - Kao CC AD - From the Departments of Molecular and Cellular Biochemistry and ckao@indiana.edu. LA - eng SI - PDB/4DEP PT - Journal Article DEP - 20160615 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (IL18R1 protein, human) RN - 0 (IL1RAP protein, human) RN - 0 (Interleukin-1 Receptor Accessory Protein) RN - 0 (Interleukin-18 Receptor alpha Subunit) SB - IM MH - HEK293 Cells MH - Humans MH - *Interleukin-1 Receptor Accessory Protein/chemistry/genetics/metabolism MH - *Interleukin-18 Receptor alpha Subunit/chemistry/genetics/metabolism MH - *Polymorphism, Genetic MH - Protein Domains MH - Signal Transduction MH - Structure-Activity Relationship PMC - PMC4974375 OTO - NOTNLM OT - cytokine OT - immunology OT - membrane protein OT - psoriasis OT - receptor structure-function OT - signal transduction EDAT- 2016/06/17 06:00 MHDA- 2017/05/06 06:00 PMCR- 2017/08/05 CRDT- 2016/06/17 06:00 PHST- 2016/02/22 00:00 [received] PHST- 2016/06/17 06:00 [entrez] PHST- 2016/06/17 06:00 [pubmed] PHST- 2017/05/06 06:00 [medline] PHST- 2017/08/05 00:00 [pmc-release] AID - S0021-9258(20)35383-7 [pii] AID - M116.723064 [pii] AID - 10.1074/jbc.M116.723064 [doi] PST - ppublish SO - J Biol Chem. 2016 Aug 5;291(32):16597-609. doi: 10.1074/jbc.M116.723064. Epub 2016 Jun 15.