Taking a Bite Out of Amyloid: Mechanistic Insights into α-Synuclein Degradation by Cathepsin L.

ABSTRACT: A common hallmark of amyloids is their resistance to an array of proteases, highlighting the difficulty in degrading these disease-related aggregated proteinaceous materials. Here, we report on the potent activity of cathepsin L (CtsL), a lysosomal protease that proteolyzes the Parkinson's disease-related amyloid formed by α-synuclein (α-syn). Using liquid chromatography with mass spectrometry and transmission electron microscopy, an elegant mechanism is revealed on the residue and ultrastructural level, respectively. Specifically, CtsL always truncates α-syn fibrils first at the C-terminus before attacking the internal β-sheet-rich region between residues 30 and 100. This suggests that only upon removal of the α-syn C-terminus can CtsL gain access to residues within the amyloid core. Inte

SUBMITTER: McGlinchey RP 

PROVIDER: S-EPMC5547998 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature