Type: | Domain | Name: | Toll/interleukin-1 receptor homology (TIR) domain |
Description: | Toll proteins or Toll-like receptors (TLRs) and the interleukin-1 receptor (IL-1R) superfamily are both involved in innate antibacterial and antifungalimmunity in insects as well as in mammals. These receptors share a conserved cytoplasmic domain of approximately 200 amino acids, known as the Toll/IL-1Rhomologous region (TIR). The similarity between TLRs and IL-1Rs is not restricted to sequence homology since these proteins also share a similarsignaling pathway. They both induce the activation of a Rel type transcription factor via an adaptor protein and a protein kinase []. Interestingly, MyD88,a cytoplasmic adaptor protein found in mammals, contains a TIR domain associated to a DEATH domain [, , ]. Besides the mammalianand Drosophila proteins, a TIR domain is also found in a number of plant cytoplasmic proteins implicated in host defense [Van der Biezen E.A., Jones J.D., Trends Biochem. Sci. 23:454-456(1998)].Site directed mutagenesis and deletion analysis have shown that the TIR domain is essential for Toll and IL-1R activities. Sequence analysis have revealed the presence of three highly conserved regions among the different members ofthe family: box 1 (FDAFISY), box 2 (GYKLC-RD-PG), and box 3 (a conserved W surrounded by basic residues). It has been proposed that boxes 1 and 2 areinvolved in the binding of proteins involved in signalling, whereas box 3 is primarily involved in directing localization of receptor, perhaps throughinteractions with cytoskeletal elements [].Resolution of the crystal structures of the TIR domains of human Toll-like receptors 1 and 2 has shown that they contain a central five-stranded parallelbeta-sheet that is surrounded by a total of five helices on both sides []. | Short Name: | TIR_dom |