A bioinformatic approach to the identification of bacterial proteins interacting with Toll-interleukin 1 receptor-resistance (TIR) homology domains.
Members of the Toll-like receptor (TLR) family are currently under intense scrutiny for their role in the sampling and recognition of pathogens. It has already been reported that both vaccinia virus and Yersinia spp. express proteins that help them evade the TLR mediated immune response, acting through the Toll-interleukin-1 receptor-resistance (TIR) domain and leucine-rich repeat region of the host TLRs respectively. The TIR domain is involved in the dimerisation of the TLRs and their complexation with their adapter molecules. We tested here the hypothesis that bacteria have the ability to secrete proteins containing similar motifs to the intracellular TIR domains that are involved in the TIR-TIR interaction necessary for the subsequent signal transmission. Based upon their sequence homology, proteins expressing TIRs have been divided into three sub-classes, based around the TLRs, the TLR adapter proteins, and the interleukin-1 and -18 adapter proteins. The highly conserved regions from these separate sub-families were then used to identify similar bacterial proteins. The bacterial proteins identified were then included in an iterative MEME-BLAST process to broaden the search. Tollip, a known TLR antagonist and adapter protein, was included in this investigation although it does not fit into any of the three sub-classes outlined above. If suitable bacterial proteins had been identified, it would signify that certain bacteria had evolved a mechanism to aid them in avoiding detection by the innate immune system acting through the TIR domains. At this stage one has to conclude that there is no evidence currently available suggesting such a mechanism, when using the strategy applied here.
Turner
Jonathan D
JD
Research Department, Bâtiment X2, Aventis Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy l'Etoile, France. jonathandavidturner@yahoo.co.uk
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000378:metabolism; D001419:Bacteria / Q000378:metabolism / Q000472:pathogenicity; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D001426:Bacterial Proteins; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors