LC-MS Reveals Isomeric Inhibition of Proteolysis by Lysosomal Cathepsins.

ABSTRACT: Defects in autophagy are implicated in many age-related diseases that cause neurodegeneration including both Alzheimer's and Parkinson's. Within autophagy, the lysosome plays a crucial role by enabling the breakdown and recycling of a wide range of biomolecular species. Herein, the effects of isomerization of aspartic acid (Asp) on substrate recognition and degradation are investigated for a collection of lysosomal cathepsins using liquid chromatography coupled to mass spectrometry. By examining a series of synthetic peptides with sequences derived from long-lived proteins known to undergo Asp isomerization, we demonstrate that isomerized forms of Asp significantly perturb cathepsin activity by impeding digestion and shifting preferential sites of proteolysis. Although the sensitivity to i

SUBMITTER: Pandey G 

PROVIDER: S-EPMC10449060 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature