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. 2021 Jul;9(7):e1707.
doi: 10.1002/mgg3.1707. Epub 2021 May 26.

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

Faisal A Alzahrani  1 , Yousef MohammedRabaa Hawsawi  2   3 , Hisham N Altayeb  1 , Naif O Alsiwiehri  4 , Othman R Alzahrani  5   6 , Hanan E Alatwi  5   6 , Osama M Al-Amer  6   7 , Suliman Alomar  8 , Lamjed Mansour  8   9
Affiliations

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

Faisal A Alzahrani et al. Mol Genet Genomic Med. 2021 Jul.

Abstract

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.

Keywords: LINE-1; MD simulation; SNPs analysis; TEX19; molecular docking.

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Conflict of interest statement

The authors have declared no conflict of interest.

Figures

FIGURE 1
FIGURE 1
3D structure of TEX19 protein. (a) The protein sequence of TEX19. (b) 3D structure. (c) Z‐scores of all protein chains in PDB, which are determined by X‐ray crystallography (light blue) or NMR spectroscopy (dark blue). (d) Validation of the developed model
FIGURE 2
FIGURE 2
Dimplot showing the interaction between the amino acids of TEX19 and LIRE1 proteins (PDB ID: 2W7A)
FIGURE 3
FIGURE 3
Molecular Dynamic Simulation of TEX19 and TIRE1 complex
FIGURE 4
FIGURE 4
TEX19 amino acid sequences conservation score among different species
FIGURE 5
FIGURE 5
Multiple sequence alignment of TEX19 gene sequences of different species showing conserved sequences in vertical lines
See this image and copyright information in PMC

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