Toll-Interleukin receptor <p>In <taxon tax_id="7227">Drosophila melanogaster</taxon> the Toll protein is involved in establishment of dorso-ventral polarity in the embryo. In addition, members of the Toll family play a key role in innate antibacterial and antifungal immunity in insects as well as in mammals. These proteins are type-I transmembrane receptors that share an intracellular 200 residue domain with the interleukin-1 receptor (IL-1R), the Toll/IL-1R homologous region (TIR). The similarity between Toll-like receptors (LTRs) and IL-1R 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 [<cite idref="PUB00005989"/>]. Interestingly, MyD88, a cytoplasmic adaptor protein found in mammals, contains a TIR domain associated to a DEATH domain (see <db_xref db="INTERPRO" dbkey="IPR000488"/>) [<cite idref="PUB00005989"/>, <cite idref="PUB00005990"/>, <cite idref="PUB00005991"/>]. Besides the mammalian and <taxon tax_id="7227">Drosophila melanogaster</taxon> proteins, a TIR domain is also found in a number of plant proteins implicated in host defence [<cite idref="PUB00005992"/>]. As MyD88, these proteins are cytoplasmic.</p><p>Site directed mutagenesis and deletion analysis have shown that the TIR domain is essential for Toll and IL-1R activities. Sequence analysis have revealedthe 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 Wsurrounded by basic residues). It has been proposed that boxes 1 and 2 areinvolved in the binding of proteins involved in signalling, whereas box 3 isprimarily involved in directing localization of receptor, perhaps throughinteractions with cytoskeletal elements [<cite idref="PUB00005993"/>].</p>