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Avicenna Journal of Medical Biotechnology، جلد ۱۳، شماره ۱، صفحات ۲۴-۳۴
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| عنوان فارسی |
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| چکیده فارسی مقاله |
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| کلیدواژه‌های فارسی مقاله |
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| عنوان انگلیسی |
Role of Phosphorylation and Hyperphosphorylation of Tau in Its Interaction with βα Dimeric Tubulin Studied from a Bioinformatics Perspective |
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| چکیده انگلیسی مقاله |
Background: Tau is a disordered Microtubule Associated Protein (MAP) which prefers to bind and stabilize microtubules. Phosphorylation of tau in particular enhances tau-tubulin interaction which otherwise detaches from tubulin during hyperphosphorylation. The reason behind their destabilization, detachment and the role of β subunit (from microtubule) and the projection domain (Tau) in microtubule stability remains elusive till date. Thus, a complete 3D structural investigation of tau protein is much needed to address these queries as the existing crystal structures are in fragments and quite limited. Methods: In this study, the modelled human tau protein was subjected to phosphorylation and hyperphosphorylation which were later considered for docking with microtubules (βα subunits-inter dimer) and vinblastine. Results: Phosphorylated tau protein interacts with both α- and β subunits. But stronger bonding was with α- compared to β subunits. Regarding β subunit, proline rich loop and projection domain actively participated in tau binding. Interestingly, hyperphosphorylation of tau increases MAP domain flexibility which ultimately results in tau detachment, the main reason behind tangle formation in Alzheimer's disease. Conclusion: This study being the first of its kind emphasizes the role of projection domain and proline rich region of β-subunit in stabilizing the tau-tubulin interaction and also the effect of hyperphosphorylation in protein-protein and protein-drug binding. |
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| کلیدواژه‌های انگلیسی مقاله |
Phosphorylation, Tau proteins, Tubulin, Vinblastine |
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| نویسندگان مقاله |
| Hrushikesh Dixit
Faculty of Biotechnology and Bioinformatics, D.Y.Patil Deemed to be University, CBD Belapur, Navi Mumbai, India
| Selvaa Kumar C
| Ruchi Chaudhary
Faculty of Biotechnology and Bioinformatics, D.Y.Patil Deemed to be University, CBD Belapur, Navi Mumbai, India
| Divya Thaker
Faculty of Biotechnology and Bioinformatics, D.Y.Patil Deemed to be University, CBD Belapur, Navi Mumbai, India
| Nikhil Gadewal
| Debjani Dasgupta
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| نشانی اینترنتی |
https://www.ajmb.org/En/Article.aspx?id=40444 |
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| زبان مقاله منتشر شده |
en |
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