1403/01/10
اباصلت حسین زاده کلاگر

اباصلت حسین زاده کلاگر

مرتبه علمی: استاد
ارکید:
تحصیلات: دکترای تخصصی
اسکاپوس:
دانشکده: دانشکده علوم پایه
نشانی:
تلفن: 01135302452

مشخصات پژوهش

عنوان
An in silico approach to investigate the source of the controversial interpretations about the phenotypic results of the human AhR-gene G1661A polymorphism
نوع پژوهش
JournalPaper
کلیدواژه‌ها
Aryl hydrocarbon receptor; rs2066853 polymorphism; protein-protein interaction; post translational modification.
سال
2016
مجله JOURNAL OF THEORETICAL BIOLOGY
شناسه DOI
پژوهشگران Younes Aftabi ، Abasalt Hosseinzadeh Colagar ، Faramarz Mehrnejad

چکیده

Aryl hydrocarbon receptor (AhR) acts as an enhancer binding ligand-activated intracellular receptor. Chromatin remodeling components and general transcription factors such as TATAbinding 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 and acetylation for AhR-K554 variant respectively at positions 544 and 560 was predicted. Our findings intensify the idea that the AhR-G1661A transition may affects AhR-TAD interactions, especially with the TBP, which influence AhRtarget genes expression. However, the previously reported flexibility of the modular TAD could act as an intervening factor, moderate the SNP effects and causes distinct outcomes in different individuals and tissues