Creation of a Molecular Band-Aid: Disease-Linked Desmoplakin Mutations Are Resistant to Calpain Cleavage

Abstract

Arrhythmogenic cardiomyopathy (ACM), a genetic disease characterized by infiltration of fibrofatty tissue into the myocardium, is typically diagnosed by sudden cardiac death. About 60% of ACM patients have variants in genes encoding proteins of the desmosome, a structure essential for cardiomyocyte coupling. Mutations in desmoplakin, a desmosomal protein, account for about 5% of variants linked to ACM. Many of these variations occur in the N-terminal third of desmoplakin at a hotspot region (residues 299-507).