Domain combination of LRR and TIR domain
Toll-like receptor (TLR) signaling is an important immune-related signaling pathways, which plays a key role in the infectious disease. TLRs contain two domains, the extracellular domain sensing the range of microbial pathogens, while the intracellular domain serving signal transduction. Through bioinformatics analyses, I found recurrent domains combinations creating the modern vertebrate TLRs, and the process streamlined the redundant TLRs. (Wu et al 2011)
Does hormone regulate the IL17R signaling ?
Interleukin-17 receptor (IL17R) is another important immune-related receptor that play key role in either infectious disease or autoimmune disease. The IL17Rs (A, B, C and E) can recognize ligands IL17s expect IL17RD. Our analysis of extracellular domains in IL17RD suggest that this subfamily is a hormone-regulated receptor rather IL17. (Wu et al 2011)
Does IL17REL negatively regulate other IL17R subfamilies ?
We found a new subfamily of IL17Rs, IL17RELs, which exist widely in vertebrates. This receptor does not possess a cytoplasmic signaling domain and may function as a potential negative regulator of other IL17R subfamilies. (Wu et al 2011)
Similarity between Myd88 and CIKS
The adaptor of IL17Rs, namely CIKS, has only one domain SEFIR among vertebrates. Through searching in basal metazoan, we found an “ancient” CIKS protein, which contains a N-terminus DEATH and a C-terminus SEFIR structurally similar to MyD88, a conserved adaptor in TLR signaling pathway. The discovery of “ancient” CIKS bridge the link between IL17R and the TLR singling pathways. (Wu et al 2011)
Bacterial SEFIR domain potentially sabotages the host immunity
The SEFIR domain is a conserved sequence segment identified in IL17Rs and their adaptor CIKS protein. Interestingly, our analysis indicated that the bacteria acquired these SEFIR protein via a horizontal gene transfer from animals and potentially sabotages the host immunity by hijacking the IL17R signaling pathways. (Wu et al 2012)