Study of Conformational and Dynamic Changes upon Phosphorylation of Proline Rich Region of Tau210-240 Peptide Using Molecular Dynamic Simulation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F21%3A00121211" target="_blank" >RIV/00216224:14740/21:00121211 - isvavai.cz</a>

Result on the web

<a href="https://www.ceitec.eu/abstract-book-2021-final-pdf/f43850" target="_blank" >https://www.ceitec.eu/abstract-book-2021-final-pdf/f43850</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Study of Conformational and Dynamic Changes upon Phosphorylation of Proline Rich Region of Tau210-240 Peptide Using Molecular Dynamic Simulation

Original language description

The conformational and dynamic changes of protein interaction regulated by posttranslational modifications such as phosphorylation of intrinsically disordered proteins (IDPs), remains challenging to elucidate. Tau, which is a well-known IDP and its phosphorylation is of particular interest because Tau is found hyperthe conformational and dynamic changes upon phosphorylation of Tau. The proline-rich motif recognized within Tau210-240 peptide directly interact with AD progression protein such as 14-3-3. Microsecond time scale molecular dynamic simulation studies performed for apo and phosphorylated residues (212PThr, 217PThr, 231PThr, 235PSer) Tau peptide210-240 using three different temperature variants (278° K, 298° K and 310° K) and two different force field parameters (AMBER99SB-ILDN and CHARMM36m) with TIP4PD water model. These four-phosphorylation causing increase in compactness. The strong salt bridges are forming with nearby lysine and arginine due to the phosphorylation, which may alter the binding of associated protein like 14-3-3 with Tau. Phosphorylation induces a strong structural transition, with Tau210 240 favouring a bent conformation. The MD simulation results were verified using NMR experimental parameters like chemical shift, 3J-coupling etc. The experimental part has been carried out by our collaborator Prof. Isabelle Landrieu.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/LTAUSA18168" target="_blank" >LTAUSA18168: Selective NMR labelling as a tool for characterization of protein complexes involved in neurodegenerative diseases.</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů