Amyloid Fibers of ?-Synuclein Catalyze Chemical Reactions

Amyloid fibers of the protein alpha-synuclein, found in Lewy body deposits, are hallmarks of Parkinson's disease. We here show that alpha-synuclein amyloids catalyze biologically relevant chemical reactions in vitro. Amyloid fibers, but not monomers, of alpha-synuclein catalyzed hydrolysis of the model ester paranitrophenyl acetate and dephosphorylation of the model phosphoester paranitrophenyl-orthophosphate. When His50 was replaced with Ala in alpha-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 alpha-synuclein fibers may be a new gain-of-function that plays a role in Parkinson's disease.