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Lookup NU author(s): Professor Tiago OuteiroORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Authors. Published by American Chemical Society.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.
Author(s): de Bruyn E, Dorn AE, Rossetti G, Fernandez C, Outeiro TF, Schulz JB, Carloni P
Publication type: Article
Publication status: Published
Journal: Journal of Chemical Information and Modeling
Year: 2024
Volume: 64
Issue: 21
Pages: 8215-8226
Print publication date: 11/11/2024
Online publication date: 27/10/2024
Acceptance date: 15/10/2024
Date deposited: 11/11/2024
ISSN (print): 1549-9596
ISSN (electronic): 1549-960X
Publisher: American Chemical Society
URL: https://doi.org/10.1021/acs.jcim.4c01172
DOI: 10.1021/acs.jcim.4c01172
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