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

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Authors

BERA Krishnendu LASORSA A. MALKI I. DUPRE E. CANTRELLE F.X. MERZOUGUI H. SINNAEVE D. HANOULLE X. HRITZ Jozef LANDRIEU I.

Year of publication 2021
Type Conference abstract
MU Faculty or unit

Central European Institute of Technology

Citation
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.
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