Characterization and Computational Investigation of Polymorphisms in the TIR Domain of the TLR4 Protein in Holsteins Raised in Turkey

Abstract

Increasing environmental temperatures as a result of climate change adversely affect livestock welfare and health. Moreover, temperatures increase the distribution and survival of parasites and infectious agents. Livestock diseases that cause significant economic losses are a worldwide concern. Toll like receptor 4 (TLR4) is an ideal marker gene candidate, due to the key role it plays in initiating the immune response against pathogens. In this study, the toll-interleukin-1 receptor (TIR) domain polymorphisms were investigated in the Turkish Holstein cattle by DNA sequencing. The effects of polymorphisms on the protein structure and function were evaluated by computational tools (I-Mutant Suite, Project Hope and PyMOL). The rs8193069 C>T polymorphism was detected in the TIR domain. The SNP causes threonine to isoleucine substitution at position 674 of the TLR4 protein which is the second amino acid of the TIR domain. The I-Mutant Suite predicted that Thr674Ile substitution can result in decreased protein stability (DDG= -0.40 Kcal/mol). Project Hope results showed that mutant and wild-type amino acids have different properties and that this can disturb the TIR domain. The Thr674Ile polymorphism observed in the TIR domain of TLR4 protein in Turkish Holstein cattle might affect the function of the TLR4 by causing physicochemical changes.