Homologies of the thyroid sodium-iodide symporter with bacterial and viral proteins

Abstract

We have demonstrated that Na⁺/l- sym-porter ( NIS ), a novel thyroid autoantigen, has local amino acid sequence homologies with the other thyroid autoantigens: Thyroglobulin (Tg), thyroid peroxidase (TPO) and thyrotropin receptor (TSH-R). These homologies concern the 4^th, 5^th, 6^th extracellular loop and the beginning of the intracel-lular tail. We have expanded our studies and found that there are significant local homologies with other 11 proteins, most of them of bacterial or viral origin (e.g., Streptococcus or Herpes). These ho-mologies concern the 2^nd and 4^th extracellular loop, and both the beginning and the end of the intra-cellular tail. These 11 homologies were retrieved by a computer-assisted search and extracted out of a database containing almost 300,000 amino acid sequences. These homologies were of magnitude greater than those concerning the three thyroid autoantigens [identities=51.1±7.3% vs 25.3±7.8% (mean±SD), p<0.001; similarities=70.6±10.7% vs 43.3±8.5%; p<0.001]. In addition, extensive, not local, homology was found with a number of unknown proteins from invertebrates (Drosophila melanogaster and Caenorhabditis elegans) and bacteria such as Bacillus subtilis and Xantho-bacter. Previously, we had found that NIS has no extensive homology with Tg or TPO or TSH-R. This is the first demonstration of both extensive and local homologies between one thyroid autoantigen (NIS) and microbiological proteins. Taken together with data of the literature on the homologies between other thyroid antigens (Tg, TPO, TSH-R) and bacteria, the homologies we have now found reinforce the view that both bacterial and viral infections may trigger autoimmune thyroid diseases.