Identification of critical regions within the TIR domain of IL-1 receptor type I |
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| Affiliation: | 1. Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, PR China;2. Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058, PR China;3. Department of Pharmacology, University of Nantong, Nantong, PR China |
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| 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 NF-κB 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 αC′ helix (Q469-E473 in mouse IL-1RI) is probably involved in heterotypic interactions of IL-1RI with IL-1RAcP or MyD88. |
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| Keywords: | IL-1 IL-1RI TIR domain NF-κB Site-directed mutagenesis Homology modeling DEAE" },{" #name" :" keyword" ," $" :{" id" :" kw0040" }," $$" :[{" #name" :" text" ," _" :" diethylaminoethyl FACS" },{" #name" :" keyword" ," $" :{" id" :" kw0050" }," $$" :[{" #name" :" text" ," _" :" fluorescence-activated cell sorting FCS" },{" #name" :" keyword" ," $" :{" id" :" kw0060" }," $$" :[{" #name" :" text" ," _" :" fetal calf serum IL" },{" #name" :" keyword" ," $" :{" id" :" kw0070" }," $$" :[{" #name" :" text" ," _" :" interleukin IL-1RI" },{" #name" :" keyword" ," $" :{" id" :" kw0080" }," $$" :[{" #name" :" text" ," _" :" IL-1 receptor type I IL-1RAcP" },{" #name" :" keyword" ," $" :{" id" :" kw0090" }," $$" :[{" #name" :" text" ," _" :" IL-1 receptor accessory protein IL-1RAPL" },{" #name" :" keyword" ," $" :{" id" :" kw0100" }," $$" :[{" #name" :" text" ," _" :" IL-1RAcP-like LPS" },{" #name" :" keyword" ," $" :{" id" :" kw0110" }," $$" :[{" #name" :" text" ," _" :" lipopolysaccharide Mal" },{" #name" :" keyword" ," $" :{" id" :" kw0120" }," $$" :[{" #name" :" text" ," _" :" MyD88 adaptor-like protein MyD88" },{" #name" :" keyword" ," $" :{" id" :" kw1120" }," $$" :[{" #name" :" text" ," _" :" myeloid differentiation primary response protein MyD88 NF-κB" },{" #name" :" keyword" ," $" :{" id" :" kw0130" }," $$" :[{" #name" :" text" ," _" :" nuclear factor kappa B PI3K" },{" #name" :" keyword" ," $" :{" id" :" kw0140" }," $$" :[{" #name" :" text" ," _" :" phosphatidylinositol 3-kinase PBS" },{" #name" :" keyword" ," $" :{" id" :" kw0150" }," $$" :[{" #name" :" text" ," _" :" phosphate-buffered saline PKB" },{" #name" :" keyword" ," $" :{" id" :" kw0160" }," $$" :[{" #name" :" text" ," _" :" protein kinase B SI" },{" #name" :" keyword" ," $" :{" id" :" kw0170" }," $$" :[{" #name" :" text" ," _" :" stimulation index TBS" },{" #name" :" keyword" ," $" :{" id" :" kw0180" }," $$" :[{" #name" :" text" ," _" :" Tris-buffered saline TILRR" },{" #name" :" keyword" ," $" :{" id" :" kw0190" }," $$" :[{" #name" :" text" ," _" :" Toll-like and IL-1R regulator TIR" },{" #name" :" keyword" ," $" :{" id" :" kw0200" }," $$" :[{" #name" :" text" ," _" :" Toll/IL-1 receptor TLR" },{" #name" :" keyword" ," $" :{" id" :" kw0210" }," $$" :[{" #name" :" text" ," _" :" Toll-like receptor WT" },{" #name" :" keyword" ," $" :{" id" :" kw0220" }," $$" :[{" #name" :" text" ," _" :" wild type. |
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