Year 2021, Volume 11 , Issue 2, Pages 1080 - 1089 2021-06-01

HnRNPA2’in LC(286-291) Domain Fibrili ve Onun D290V Mutasyonu Hakkında Teorik Bir Çalışma
A Theorotical Study bout LC(286-291) Domain of hnRNPA2 and its D290V Mutation

Hakan ALICI [1]


Son zamanlarda, hnRNPA'lerin işlevindeki bozukluklar başta amiyotrofik lateral skleroz (ALS) ve frontotemporal demans (FTD) olmak üzere birçok nörodejeneratif hastalıklar ile ilişkilendirilmektedir. hnRNPA'lerin düşük karmaşıklık (LC) domainlerinin fibrilleşme eğilimlerinin bu işlev bozukluklarının temel nedeni olduğu düşünülmektedir. Bu çalışmada atomik yapısı çok yakın zamanda ortaya konulmuş D290V mutasyonuna sahip hnRNPA2'nin LC(286-291) fibril domaininin bir polimorfu (pdb kod:6WPQ) ve bu poliformun mutasyonsuz yani vahşi tip (WT) fibril formu hakkında bir moleküler Dinamik (MD) simülasyon çalışması sunuyoruz. MD simulasyon sonuçlarına göre önerilen fibril polimorf yapısı için D290V mutasyonun kararlı bir konformasyona sahip olduğu ancak onun WT formun bu fibril polimorf yapı konformasyonu için kararsız olduğu tespit edilmiştir. Sonuç olarak çalışmada elde edilen bulgular gelecekteki muhtemel ilaç çalışmaları için yalnızca D290V fibril yapısının hedef yapı olarak ele alınabileceğini işaret etmektedir.
Recently, disorders in the function of hnRNPAs have been associated with many neurodegenerative diseases, especially amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In addition, the fibrillation tendency of the low complexity (LC) domains of hnRNPAs is thought to be the root cause of these dysfunctions. In this paper, we present a molecular dynamic (MD) simulation study for the recently crystalized a fibril polymorph of the LC (286-291) domain (pdb id:6WPQ) of hnRNPA2 with the D290V mutation and its wild-type (WT) fibril form, that is no mutation. According to the MD simulation results, it was detected that fibril polymorph with D290V mutation has stable conformations, but WT is unstable for this fibril polymorph. As a result, the findings of the study indicate that only the D290V fibril structure can be considered as the target structure for possible future drug studies.
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Primary Language tr
Subjects Science, Physics, Applied
Published Date Haziran-2021
Journal Section Fizik / Physics
Authors

Orcid: 0000-0001-5105-8331
Author: Hakan ALICI (Primary Author)
Institution: ZONGULDAK BÜLENT ECEVİT ÜNİVERSİTESİ
Country: Turkey


Supporting Institution Zonguldak Bülent Ecevit Üniversitesi
Project Number 2015-22794455-03
Thanks Bu çalışmaya 2015-22794455-03 nolu Altyapı Projesi ile maddi kaynak sağlayan Zonguldak Bülent Ecevit Üniversitesi Bilimsel Araştırmalar Proje Birimi’ne teşekkür ederiz.
Dates

Application Date : December 22, 2020
Acceptance Date : February 5, 2021
Publication Date : June 1, 2021

Bibtex @research article { jist845090, journal = {Journal of the Institute of Science and Technology}, issn = {2146-0574}, eissn = {2536-4618}, address = {}, publisher = {Igdir University}, year = {2021}, volume = {11}, pages = {1080 - 1089}, doi = {10.21597/jist.845090}, title = {HnRNPA2’in LC(286-291) Domain Fibrili ve Onun D290V Mutasyonu Hakkında Teorik Bir Çalışma}, key = {cite}, author = {Alıcı, Hakan} }
APA Alıcı, H . (2021). HnRNPA2’in LC(286-291) Domain Fibrili ve Onun D290V Mutasyonu Hakkında Teorik Bir Çalışma . Journal of the Institute of Science and Technology , 11 (2) , 1080-1089 . DOI: 10.21597/jist.845090
MLA Alıcı, H . "HnRNPA2’in LC(286-291) Domain Fibrili ve Onun D290V Mutasyonu Hakkında Teorik Bir Çalışma" . Journal of the Institute of Science and Technology 11 (2021 ): 1080-1089 <https://dergipark.org.tr/en/pub/jist/issue/61423/845090>
Chicago Alıcı, H . "HnRNPA2’in LC(286-291) Domain Fibrili ve Onun D290V Mutasyonu Hakkında Teorik Bir Çalışma". Journal of the Institute of Science and Technology 11 (2021 ): 1080-1089
RIS TY - JOUR T1 - HnRNPA2’in LC(286-291) Domain Fibrili ve Onun D290V Mutasyonu Hakkında Teorik Bir Çalışma AU - Hakan Alıcı Y1 - 2021 PY - 2021 N1 - doi: 10.21597/jist.845090 DO - 10.21597/jist.845090 T2 - Journal of the Institute of Science and Technology JF - Journal JO - JOR SP - 1080 EP - 1089 VL - 11 IS - 2 SN - 2146-0574-2536-4618 M3 - doi: 10.21597/jist.845090 UR - https://doi.org/10.21597/jist.845090 Y2 - 2021 ER -
EndNote %0 Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi HnRNPA2’in LC(286-291) Domain Fibrili ve Onun D290V Mutasyonu Hakkında Teorik Bir Çalışma %A Hakan Alıcı %T HnRNPA2’in LC(286-291) Domain Fibrili ve Onun D290V Mutasyonu Hakkında Teorik Bir Çalışma %D 2021 %J Journal of the Institute of Science and Technology %P 2146-0574-2536-4618 %V 11 %N 2 %R doi: 10.21597/jist.845090 %U 10.21597/jist.845090
ISNAD Alıcı, Hakan . "HnRNPA2’in LC(286-291) Domain Fibrili ve Onun D290V Mutasyonu Hakkında Teorik Bir Çalışma". Journal of the Institute of Science and Technology 11 / 2 (June 2021): 1080-1089 . https://doi.org/10.21597/jist.845090
AMA Alıcı H . HnRNPA2’in LC(286-291) Domain Fibrili ve Onun D290V Mutasyonu Hakkında Teorik Bir Çalışma. Iğdır Üniv. Fen Bil Enst. Der.. 2021; 11(2): 1080-1089.
Vancouver Alıcı H . HnRNPA2’in LC(286-291) Domain Fibrili ve Onun D290V Mutasyonu Hakkında Teorik Bir Çalışma. Journal of the Institute of Science and Technology. 2021; 11(2): 1080-1089.
IEEE H. Alıcı , "HnRNPA2’in LC(286-291) Domain Fibrili ve Onun D290V Mutasyonu Hakkında Teorik Bir Çalışma", Journal of the Institute of Science and Technology, vol. 11, no. 2, pp. 1080-1089, Jun. 2021, doi:10.21597/jist.845090