Hypertrophic cardiomyopathy-linked alpha-cardiac actin mutations and their role on actomyosin interactions

Abstract

Mutations in genes encoding sarcomeric proteins are linked to changes in the myocardium which can manifest as hypertrophic cardiomyopathy (HCM). Three α-cardiac actin (ACTC) gene mutations (R95C, F90Δ, and H88Y) associated with HCM, are located in subdomain 1 of actin at the actomyosin interface. Cyclic interactions between actin and myosin result in contraction. The duty ratio, r, is the fraction of time spent by actin and myosin interacting. My hypothesis is that mutations in subdomain 1 of actin increase the duty ratio allowing for HCM development. The duty ratio for the R95C ACTC variant was found to be higher than bovine actin while F90Δ and H88Y were lower. Further investigation revealed that the DNase-I purification affected the activity of the ACTC variants. Therefore, the r for the ACTC variants may be unreliable; hence, I cannot confidently determine the mechanism used by the ACTC variants leading HCM development.