Preprint

FZJ-2023-01834

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Impact of Phosphorylation on alpha-Synuclein Structural Determinants

Dorn, A.FZJ* ; de Bruyn, E.FZJ* ; Rossetti, G. (Corresponding author)FZJ* ; Fernandez, C. ; Outeiro, T. F. ; Schulz, J. B.FZJ* ; Carloni, P.FZJ*

2023
Cold Spring Harbor Laboratory, NY Cold Spring Harbor

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Please use a persistent id in citations: http://hdl.handle.net/2128/34309  doi:10.1101/2023.03.10.531864

Abstract: Serine 129 and, to a lesser extent, serine 87 can appear phosphorylated in the intrinsically disordered protein human α-synuclein (AS), a key player in Parkinson’s disease, where it accumulates in proteinaceous aggregates. Intriguingly, both phosphorylations are located in a highly negative potential region of the protein. Here we used molecular simulation to provide insight in the selective phosphorylation by polo-like kinase 2 (PLK2), in both monomeric and fibrillar forms of AS. We suggest that phosphorylation does not impact on the structural determinants of the physiological AS conformational ensemble, as the phosphate group is mostly solvated. Our findings are consistent with experimental data on the non-acetylated, non-physiological form of the protein. The phosphate groups of pAS may be solvated also in the aggregated form.

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Contributing Institute(s):

1. Jülich Supercomputing Center (JSC)
2. Computational Biomedicine (IAS-5)
3. Computational Biomedicine (INM-9)
4. JARA-BRAIN (JARA-BRAIN)

Research Program(s):

1. 5111 - Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)
2. HDS LEE - Helmholtz School for Data Science in Life, Earth and Energy (HDS LEE) (HDS-LEE-20190612) (HDS-LEE-20190612)

Appears in the scientific report 2023

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Database coverage:

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