In silico modeling of the interaction between TEX19 and LIRE1, and analysis of TEX19 gene missense SNPs

Background: Testis expressed 19 (TEX19) is a specific human stem cell gene identified as cancer-testis antigen (CTA), which emerged as a potential therapeutic drug target. TEX19.1, a mouse paralog of human TEX19, can interact with LINE-1 retrotransposable element ORF1 protein (LIRE1) and subsequently restrict mobilization of LINE-1 elements in the genome. Aim: This study aimed to predict the interaction of TEX19 with LIRE1 and analyze TEX19 missense polymorphisms. TEX19 model was generated using I-TASSER and the interaction between TEX19 and LIRE1 was studied using the HADDOCK software. Methods: The stability of the docking formed complex was studied through the molecular dynamic simulation using GROMACS. Missense SNPs (n=102) of TEX19 were screened for their potential effects on protein structure and function using different software. Results: Outcomes of this study revealed amino acids that potentially stabilize the predicted interaction interface between TEX19 and LIRE1. Of these SNPs, 37 were predicted to play a probably damaging role for the protein, three of them (F35S, P61R, and E55L) located at the binding site of LIRE1 and could disturb this binding affinity. Conclusion: This information can be verified by further in vitro and in vivo experimentations and could be exploited for potential therapeutic targets.

Automated summary

This study predicted the interaction between TEX19 and LIRE1, as well as analyzed missense polymorphisms of TEX19 using computational methods. The results identified amino acids that may disturb the binding affinity between TEX19 and LIRE1, suggesting potential implications for therapeutic targets.