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

Kód výsledku v 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>

Výsledek na webu

<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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Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LTAUSA18168" target="_blank" >LTAUSA18168: Selektivní NMR značení jako nástroj pro charakterizaci proteinových komplexů zapojených do neurodegenerativních onemocnění</a><br>

Návaznosti

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

Rok uplatnění

2021

Kód důvěrnosti údajů

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