Molecular Forces Governing the Biological Function of Per-Arnt-Sim-B (PAS-B) Domains: A Comparative Computational Study
| العنوان: | Molecular Forces Governing the Biological Function of Per-Arnt-Sim-B (PAS-B) Domains: A Comparative Computational Study |
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| المؤلفون: | Piotr Zaborniak, Ruidi Zhu, Sylvia Reznikov, Matthew Kondal, João V de Souza, Agnieszka K. Bronowska |
| المصدر: | Biophysica Volume 1 Issue 1 Pages 1-14 |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | D. Suzukii, 0301 basic medicine, Aryl hydrocarbon receptor nuclear translocator, Computational biology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, cysteinome, medicine, Transcriptional regulation, HIF1α, Receptor, Drosophila suzukii, Transcription factor, General Environmental Science, Mutation, biology, aryl hydrocarbon receptor, Chemistry, molecular dynamics simulations, Aryl hydrocarbon receptor, biology.organism_classification, Small molecule, 030104 developmental biology, Per-Arnt-Sim, biology.protein, General Earth and Planetary Sciences, NCOA1, HIF2α, 030217 neurology & neurosurgery |
| الوصف: | Per-Arnt-Sim (PAS) domains are evolutionarily-conserved regions found in proteins in all living systems, involved in transcriptional regulation and the response to hypoxic and xenobiotic stress. Despite having low primary sequence similarity, they show an impressively high structural conservation. Nonetheless, understanding the underlying mechanisms that drive the biological function of the PAS domains remains elusive. In this work, we used molecular dynamics simulations and bioinformatics tools in order the investigate the molecular characteristics that govern the intrinsic dynamics of five PAS-B domains (human AhR receptor, NCOA1, HIF1α, and HIF2α transcription factors, and Drosophila Suzukii (D. Suzukii) juvenile hormone receptor JHR). First, we investigated the effects of different length of N and C terminal regions of the AhR PAS-B domain, showing that truncation of those segments directly affects structural stability and aggregation propensity of the domain. Secondly, using the recently annotated PAS-B located in the methoprene-tolerant protein/juvenile hormone receptor (JHR) from D. Suzukii, we have shown that the mutation of the highly conserved “gatekeeper” tyrosine to phenylalanine (Y322F) does not affect the stability of the domain. Finally, we investigated possible redox-regulation of the AhR PAS-B domain by focusing on the cysteinome residues within PAS-B domains. The cysteines in AhR PAS-B are directly regulating the dynamics of the small molecule ligand-gating loop (residues 305 to 326). In conclusion, we comprehensibly described several molecular features governing the behaviour of PAS-B domains in solution, which may lead to a better understanding of the forces driving their biological functions. |
| وصف الملف: | application/pdf |
| تدمد: | 2673-4125 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e316a4a2355483050c3d582299a788b5 https://doi.org/10.3390/biophysica1010001 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e316a4a2355483050c3d582299a788b5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 26734125 |
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