title: An extensively associated dimer in the structure of the C713S mutant of the TIR domain of human TLR2.
abstract: The Toll/interleukin-1 receptor (TIR) domains are conserved modules in the intracellular regions of the Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). The domains are crucial for the signal transduction by these receptors, through homotypic interactions among the receptor and the downstream adapter TIR domains. Previous studies showed that the BB loop in the structure of the TIR domain forms a prominent conserved feature on the surface and is important for receptor signaling. Here we report the crystal structure of the C713S mutant of the TIR domain of human TLR2. An extensively associated dimer is observed in the crystal structure and mutations of several residues in this dimer interface abolished the function of the receptor. Moreover, the structure shows that the BB loop can adopt different conformations, which are required for the formation of this dimer. This asymmetric dimer might represent the TLR2:TLRx heterodimer in the function of this receptor.
authors.affiliation: Department of Biological Sciences, Columbia University, 10027, New York, NY, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Tao
authors.forename: Yingwu
authors.initials: Y
authors.lastname: Xu
authors.forename: Ye
authors.initials: Y
authors.lastname: Zheng
authors.forename: Amer A
authors.initials: AA
authors.lastname: Beg
authors.forename: Liang
authors.initials: L
authors.lastname: Tong
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D029721:Drosophila Proteins; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
chemical_list: D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors