Radons, Juergen and Falk, Werner and Dove, Stefan (2015) Identification of critical regions within the TIR domain of IL-1 receptor type I. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 68. pp. 15-20. ISSN 1357-2725, 1878-5875
Full text not available from this repository. (Request a copy)Abstract
Interleukin-1 receptor type I (IL-1RI) belongs to a superfamily of proteins characterized by an intracellular Toll/IL-1 receptor (TIR) domain. This domain harbors three conserved regions called boxes 1-3 that play crucial roles in mediating IL-1 responses. Boxes 1 and 2 are considered to be involved in binding of adapter molecules. Amino acids possibly crucial for IL-1RI signaling were predicted via homology models of the IL-1RI TIR domain based on the crystal structure of IL-1RAPL. The role of ten of these residues was investigated by site-directed mutagenesis and a functional luciferase assay reflecting NFKB activity in transiently transfected Jurkat cells. In particular, the mutants E437K/D438K, E472A/E473A and S465A/S470A/S471A/E472A/E473A showed decreased and the mutant E437A/D438A increased IL-1 responsiveness compared to the mouse IL-1RI wild type. In conclusion, the alpha C' helix (Q469-E473 in mouse IL-1RI) is probably involved in heterotypic interactions of IL-1RI with IL-1RAcP or MyD88. (C) 2015 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TOLL-LIKE RECEPTORS; NF-KAPPA-B; INTERLEUKIN-1 RECEPTOR; ACCESSORY PROTEIN; SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURE; INTERACTION SITES; ACTIVATION; INFLAMMATION; MYD88; IL-1; IL-1RI; TIR domain; NF-kappa B; Site-directed mutagenesis; Homology modeling |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 May 2019 08:57 |
| Last Modified: | 06 May 2019 08:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4525 |
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