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Amyloid Fibers of α-Synuclein Catalyze Chemical Reactions.

ABSTRACT: Amyloid fibers of the protein α-synuclein, found in Lewy body deposits, are hallmarks of Parkinson's disease. We here show that α-synuclein amyloids catalyze biologically relevant chemical reactions in vitro. Amyloid fibers, but not monomers, of α-synuclein catalyzed hydrolysis of the model ester para-nitrophenyl acetate and dephosphorylation of the model phosphoester para-nitrophenyl-orthophosphate. When His50 was replaced with Ala in α-synuclein, dephosphorylation but not esterase activity of amyloids was diminished. Truncation of the protein's C-terminus had no effect on fiber catalytic efficiency. Catalytic activity of α-synuclein fibers may be a new gain-of-function that plays a role in Parkinson's disease.

SUBMITTER: Horvath I

PROVIDER: S-EPMC9936539 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Amyloid Fibers of α-Synuclein Catalyze Chemical Reactions.

Horvath Istvan I Wittung-Stafshede Pernilla P

ACS chemical neuroscience 20230206 4

Amyloid fibers of the protein α-synuclein, found in Lewy body deposits, are hallmarks of Parkinson's disease. We here show that α-synuclein amyloids catalyze biologically relevant chemical reactions in vitro. Amyloid fibers, but not monomers, of α-synuclein catalyzed hydrolysis of the model ester <i>para</i>-nitrophenyl acetate and dephosphorylation of the model phosphoester <i>para</i>-nitrophenyl-orthophosphate. When His50 was replaced with Ala in α-synuclein, dephosphorylation but not esteras ...[more]

PMID: 36745416

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