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In Silico Modeling Of The Interaction Between Tex19 And Lire1, And Analysis Of Tex19 Gene Missense Snps

MOLECULAR GENETICS & GENOMIC MEDICINE(2021)

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摘要
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.
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关键词
LINE-1, MD simulation, molecular docking, SNPs analysis, TEX19
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