title: Recent insights into the structure of Toll-like receptors and post-translational modifications of their associated signalling proteins.
abstract: TLRs (Toll-like receptors) are essential modulators of the innate immune response through their ability to respond to a diverse range of conserved structures within microbes. Recent advances have been made in our understanding of the initiation of TLR signals as a result of the elucidation of crystal structures of TLRs interacting with their ligands. Most notably the structure of TLR1/2 with triacylated lipopeptide and TLR4 in a complex with LPS (lipopolysaccharide) and MD2 has been solved. These explain the basis for TLR dimerization which initiates signalling. Modifications of TLRs and their receptor proximal signalling proteins have also been uncovered. Phosphorylation of adaptor proteins and ubiquitination (both Lys48- and Lys63-linked) of TLRs, IRAKs (interleukin-1 receptor-associated kinase), Pellinos and TRAF6 (tumour-necrosis-factor-receptor-associated factor 6) have been described, which promote signalling and lead to signal termination. A detailed molecular account of the initiation and termination of TLR signalling is presented.
authors.affiliation: School of Biochemistry and Immunology, Trinity College Dublin, Ireland. carpents@tcd.ie
authors.forename: Susan
authors.initials: S
authors.lastname: Carpenter
authors.forename: Luke A J
authors.initials: LA
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008024:Ligands; D051193:Toll-Like Receptors