Structure, function and regulation of the Toll/IL-1 receptor adaptor proteins.
The Toll/IL-1 receptor (TIR) domain plays a central role in Toll-like receptor (TLR) signalling. All TLRs contain a cytoplasmic TIR domain, which, upon activation, acts as a scaffold to recruit adaptor proteins. The adaptor proteins MyD88, Mal, TRIF, TRAM and SARM are also characterized by the presence of a TIR domain. MyD88, Mal, TRIF and TRAM associate with the TLRs via homophilic TIR domain interactions whereas SARM utilizes its TIR domain to negatively regulate TRIF. It is well established that the differential recruitment of adaptors to TLRs provides a significant amount of specificity to the TLR-signalling pathways. Despite this, the TIR-TIR interface has not been well defined. However, structural studies have indicated the importance of TIR domain surfaces in mediating specific TIR-TIR interactions. Furthermore, recent findings regarding the regulation of adaptors provide further insight into the crucial role of the TIR domain in TLR signalling.
School of Biochemistry and Immunology, Trinity College, Dublin, Ireland. wattert@tcd.ie
Tanya M
TM
Watters
Elaine F
EF
Kenny
Luke A J
LA
O'Neill
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008024:Ligands; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000737:chemistry* / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D008024:Ligands; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors