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

Faisal A Alzahrani; Yousef MohammedRabaa Hawsawi; Hisham N Altayeb; Naif O Alsiwiehri; Othman R Alzahrani; Hanan E Alatwi; Osama M Al-Amer; Suliman Alomar; Lamjed Mansour

doi:10.1002/mgg3.1707

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

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

Authors

Faisal A Alzahrani¹, Yousef MohammedRabaa Hawsawi^{2

3}, Hisham N Altayeb¹, Naif O Alsiwiehri⁴, Othman R Alzahrani^{5

6}, Hanan E Alatwi^{5

6}, Osama M Al-Amer^{6

7}, Suliman Alomar⁸, Lamjed Mansour^{8

9}

Affiliations

¹ Department of Biochemistry, Faculty of Science, Embryonic Stem Cell Unit, King Fahad Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia.
² Research Center at King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia.
³ College of Medicine, Al-Faisal University, Riyadh, Saudi Arabia.
⁴ Department of Clinical Laboratory Science, Faculty of Applied Medical Science, Taif University, Taif, Saudi Arabia.
⁵ Department of Biology, Faculty of Sciences, University of Tabuk, Tabuk, Saudi Arabia.
⁶ Genome and Biotechnology Unit, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia.
⁷ Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabouk, Tabuk, Saudi Arabia.
⁸ Doping Research Chair, Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
⁹ Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Humans
Molecular Docking Simulation*
Mutation, Missense*
Polymorphism, Single Nucleotide
Protein Binding
RNA-Binding Proteins* / chemistry
RNA-Binding Proteins* / genetics
RNA-Binding Proteins* / metabolism

Substances

RNA-Binding Proteins
Tex19 protein, human
L1RE1 protein, human