Structural highlights
FunctionPublication Abstract from PubMedToll-like receptors (TLRs) activate innate immunity in response to pathogen-associated molecular patterns (PAMPs). The ectodomain of a TLR directly senses a PAMP and the intracellular TIR domain dimerizes to initiate a signaling cascade. The TIR domains of TLR6 and TLR10, which belong to the TLR1 subfamily, have been structurally characterized in a dimer, whereas those of other subfamilies, including TLR15, have not been explored at the structural or molecular level. TLR15 is a TLR unique to birds and reptiles that responds to virulence-associated fungal and bacterial proteases. To reveal how the TLR15 TIR domain (TLR15(TIR)) triggers signaling, the crystal structure of TLR15(TIR) was determined in a dimeric form and a mutational study was performed. TLR15(TIR) forms a one-domain structure in which a five-stranded beta-sheet is decorated by alpha-helices, as shown for TLR1 subfamily members. TLR15(TIR) exhibits substantial structural differences from other TLRs at the BB and DD loops and alphaC2 helix that are involved in dimerization. As a result, TLR15(TIR) is likely to form a dimeric structure that is unique in its intersubunit orientation and the contribution of each dimerizing region. Further comparative analysis of TIR structures and sequences provides insights into the recruitment of a signaling adaptor protein by TLR15(TIR). Structural analysis of the Toll-like receptor 15 TIR domain.,Ko KY, Song WS, Park J, Lee GS, Yoon SI IUCrJ. 2023 May 1;10(Pt 3):352-362. doi: 10.1107/S2052252523002956. PMID:37079400[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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