TY  - EJOUR
AU  - Dorn, Anton
AU  - de Bruyn, Emile
AU  - Rossetti, Giulia
AU  - Fernandez, Claudio
AU  - Outeiro, Tiago F.
AU  - Schulz, Jörg B.
AU  - Carloni, Paolo
TI  - Impact of Phosphorylation on alpha-Synuclein Structural Determinants
JO  - bioRxiv beta
CY  - Cold Spring Harbor
PB  - Cold Spring Harbor Laboratory, NY
M1  - FZJ-2023-01834
PY  - 2023
AB  - 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.
LB  - PUB:(DE-HGF)25
DO  - DOI:10.1101/2023.03.10.531864
UR  - https://juser.fz-juelich.de/record/1006781
ER  -