Journal Article

FZJ-2024-06053

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Impact of Phosphorylation on the Physiological Form of Human alpha-Synuclein in Aqueous Solution

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

2024
American Chemical Society Washington, DC

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Please use a persistent id in citations: doi:10.1021/acs.jcim.4c01172  doi:10.34734/FZJ-2024-06053

Abstract: Serine 129 can be phosphorylated in pathological inclusions formed by the intrinsically disordered protein human α-synuclein (AS), a key player in Parkinson’s disease and other synucleinopathies. Here, molecular simulations provide insight into the structural ensemble of phosphorylated AS. The simulations allow us to suggest that phosphorylation significantly impacts the structural content of the physiological AS conformational ensemble in aqueous solution, as the phosphate group is mostly solvated. The hydrophobic region of AS contains β-hairpin structures, which may increase the propensity of the protein to undergo amyloid formation, as seen in the nonphysiological (nonacetylated) form of the protein in a recent molecular simulation study. Our findings are consistent with existing experimental data with the caveat of the observed limitations of the force field for the phosphorylated moiety.

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Contributing Institute(s):

1. Computational Biomedicine (INM-9)
2. Jülich Supercomputing Center (JSC)
3. Jara-Institut Quantum Information (INM-11)

Research Program(s):

1. 5111 - Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)
2. 5112 - Cross-Domain Algorithms, Tools, Methods Labs (ATMLs) and Research Groups (POF4-511) (POF4-511)
3. HDS LEE - Helmholtz School for Data Science in Life, Earth and Energy (HDS LEE) (HDS-LEE-20190612) (HDS-LEE-20190612)
4. SFB 1286 B08 - Definition von Kaskaden molekularer Veränderungen bei Synucleinopathien während der Neurodegeneration (B08) (386961151) (386961151)
5. DFG project G:(GEPRIS)390729940 - EXC 2067: Multiscale Bioimaging: Von molekularen Maschinen zu Netzwerken erregbarer Zellen (390729940) (390729940)
6. DFG project G:(GEPRIS)491111487 - Open-Access-Publikationskosten / 2025 - 2027 / Forschungszentrum Jülich (OAPKFZJ) (491111487) (491111487)

Appears in the scientific report 2024

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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