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

BERA, Krishnendu, A. LASORSA, I. MALKI, E. DUPRE, F.X. CANTRELLE, H. MERZOUGUI, D. SINNAEVE, X. HANOULLE, Jozef HRITZ and I. LANDRIEU. Study of Conformational and Dynamic Changes upon Phosphorylation of Proline Rich Region of Tau210-240 Peptide Using Molecular Dynamic Simulation. 2021.

Basic information

• Original name: Study of Conformational and Dynamic Changes upon Phosphorylation of Proline Rich Region of Tau210-240 Peptide Using Molecular Dynamic Simulation
• Authors: BERA, Krishnendu (356 India, belonging to the institution), A. LASORSA, I. MALKI, E. DUPRE, F.X. CANTRELLE, H. MERZOUGUI, D. SINNAEVE, X. HANOULLE, Jozef HRITZ (703 Slovakia, belonging to the institution) and I. LANDRIEU.
• Edition: 2021.

Other information

• Original language: English
• Type of outcome: Conference abstract
• Field of Study: 10608 Biochemistry and molecular biology
• Country of publisher: Czech Republic
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• RIV identification code: RIV/00216224:14740/21:00121211
• Organization unit: Central European Institute of Technology
• Keywords in English: Molecular Dynamic Simulation; Tau210-240
• Tags: rivok

Abstract

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.

Links

• LTAUSA18168, research and development project: Name: Selektivní NMR značení jako nástroj pro charakterizaci proteinových komplexů zapojených do neurodegenerativních onemocnění

Investor: Ministry of Education, Youth and Sports of the CR, Selective NMR labelling as a tool for characterization of protein complexes involved in neurodegenerative diseases., INTER-ACTION