| Primary Identifier | IPR035897 | Type | Homologous_superfamily |
| Short Name | Toll_tir_struct_dom_sf |
| description | Toll proteins or Toll-like receptors (TLRs) and the interleukin-1 receptor (IL-1R) superfamily areboth 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-1R homologous region (TIR). The similarity between TLRs and IL-1Rs is not restricted to sequence homology since these proteins also share a similar signalling 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 mammalian and Drosophila proteins, a TIR domain is also found in a number of plant cytoplasmic proteins implicated in host defense [].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 of the 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 are involved in the binding of proteins involved in signalling, whereas box 3 is primarily involved in directing localization of receptor, perhaps through interactions with cytoskeletal element [].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 parallel β-sheet that is surrounded by a total of five helices on both sides, with connecting loop structures []. The loop regions appear to play an important role in mediating the specificity of protein-proteininteractions [, ]. |
