Supplementary methods:

16 TIR domain sequences from Homo sapiens (as listed below) were used as seeds in PSI-BLAST searches via the NCBI BLAST interface at http://blast.ncbi.nlm.nih.gov against the non-redundant protein database to investigate TIR domain distribution in bacteria, fungi, archaea and viruses. Default search parameters were used until no new results were returned with an e-value cut-off of 0.005. Results were filtered for proteins from whole bacterial, archaeal, fungal or viral genomes and de-duplicated using the “my xBASE” component of xBASE 1. Results from subgenomic fragments in nr (e.g. deposits of single proteins) were removed. Additional PSI-BLAST searches were run using the parameters described above with TIR domain sequences from other species (see list on next page). This increased the unique bacterial results so the resulting list of TIR domain proteins in bacteria is not exhaustive.

Reference List

1 Chaudhuri,R.R. et al. (2008) xBASE2: a comprehensive resource for comparative bacterial genomics. Nucl. Acids Res. 36, D543-D546

Protein seed / Protein ID
Residues 639 - 775 from TLR1, Homo sapiens / CAG38593
Residues 643 - 784 from TLR2, Homo sapiens / AAH33756
Residues 758 - 862 from TLR3, Homo sapiens / AAH59372
Residues 636 - 774 from TLR4, Homo sapiens / CAH72619
Residues 695 - 832 from TLR5, Homo sapiens / AAI09119
Residues 644 - 780 from TLR6, Homo sapiens / BAA78631
Residues 893 - 1034 from TLR7, Homo sapiens / AAQ88659
Residues 882 - 1020 from TLR8, Homo sapiens / AAQ88663
Residues 872 - 1009 from TLR9, Homo sapiens / AAQ89443
Residues 636 - 774 from TLR10, Homo sapiens / AAQ88667
Residues 86 - 168 from TIRAP[1], Homo sapiens / NP_001034750
Residues 395 - 527 from TRIF[2], Homo sapiens / BAC44839
Residues 81 - 174 from TRAM[3], Homo sapiens / AAO74498
Residues 176 - 305 from MyD88[4], Homo sapiens / NP_002459
Residues 561 - 700 from Sarm1[5], Homo sapiens / NP_055892
Residues 167 - 304 from SIGIRR[6], Homo sapiens / CAG33619
Residues 821 - 915 from TirA, Dictyostelium discoideum AX4 / XP_636358
Residues 578 - 718 from Tir-1, Caenorhabditis elegans / NP_001021253

[1] Toll-interleukin 1 receptor domain-containing adaptor protein

[2] TIR domain containing adaptor inducing interferon-beta

[3] TRIF-related adaptor molecule

[4] myeloid differentiation primary response gene 88

[5] sterile alpha and TIR motif containing 1

[6] single Ig IL-1R-related molecule