Amyloid Fibers of α-Synuclein Catalyze Chemical Reactions
Journal article, 2023

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.

catalytic efficiency

α-synuclein

Catalysis

Parkinson’s disease

amyloid fibers

Author

Istvan Horvath

Chalmers, Life Sciences, Chemical Biology

Pernilla Wittung Stafshede

Chalmers, Life Sciences, Chemical Biology

ACS Chemical Neuroscience

1948-7193 (eISSN)

Vol. 14 4 603-608

Subject Categories

Biochemistry and Molecular Biology

Biocatalysis and Enzyme Technology

Organic Chemistry

DOI

10.1021/acschemneuro.2c00799

PubMed

36745416

More information

Latest update

3/15/2023