An in silico approach to investigate the source of the controversial interpretations about the phenotypic results of the human AhR-gene G1661A polymorphism

Journal of Theoretical Biology
Younes AftabiFaramarz Mehrnejad

Abstract

Aryl hydrocarbon receptor (AhR) acts as an enhancer binding ligand-activated intracellular receptor. Chromatin remodeling components and general transcription factors such as TATA-binding protein (TBP) are evoked on AhR-target genes by interaction with its flexible transactivation domain (TAD). AhR-G1661A single nucleotide polymorphism (SNP: rs2066853) causes an arginine to lysine substitution in the acidic sub-domain of TAD at position 554 (R554K). Although, numerous studies associate the SNP with some abnormalities such as cancer, other reliable investigations refuse the associations. Consequently, the interpretation of the phenotypic results of G1661A-transition has been controversial. In this study, an in silico analysis were performed to investigate the possible effects of the transition on AhR-mRNA, protein structure, interaction properties and modifications. The analysis revealed that the R554K substitution affects secondary structure and solvent accessibility of adjacent residues. Also, it causes to decreasing of the AhR stability; altering the hydropathy features of the local sequence and changing the pattern of the residues at the binding site of the TAD-acidic sub-domain. Generating of new sites for ubiquitination an...Continue Reading

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Citations

Jun 22, 2017·Hormones & Cancer·Robert Formosa, Josanne Vassallo
May 5, 2018·Human Molecular Genetics·Yu ZhouZhenglin Yang
Sep 1, 2019·International Journal of Molecular Sciences·Deborah MinzaghiSandrine Dubrac
Dec 23, 2016·Pathology Oncology Research : POR·Zahra SoleimaniYounes Aftabi
Jun 9, 2017·Environmental Science and Pollution Research International·Gholam Ali JosarayiAbasalt Hosseinzadeh Colagar
Jul 18, 2017·Environmental Science and Pollution Research International·Younes AftabiEmadoddin Moudi
Feb 6, 2017·Environmental Science and Pollution Research International·Taymour MostafaBolis S Gendy
Dec 8, 2020·Frontiers in Endocrinology·Agnese ReSalvatore Cannavò
Oct 12, 2021·Nucleosides, Nucleotides & Nucleic Acids·Tahereh ZahediJahan-Bakhsh Raoof

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