The Dark Side of Actin: characterization of hypertrophic cardiomyopathy linked S271F ACTC variant and dilated cardiomyopathy linked T126I ACTC variant
Cardiomyopathy is a commonly inherited cardiovascular disease that affect the heart muscle. Two types of cardiomyopathy include hypertrophic cardiomyopathy (HCM), where the left ventricle is thickened, and dilated cardiomyopathy (DCM), where left ventricle is thinned out. Mutations in genes that code for contractile proteins, such as α-cardiac actin (ACTC) has been linked to HCM or DCM. This thesis investigates two ACTC variants that have never been studied before: S271F, an HCM-linked ACTC variant and T126I, an DCM-linked ACTC variant. Both variants are located on the backside of the traditional ribbon diagram of actin; what I call the “dark side” of actin. Both variants were biochemically characterized. The S271F ACTC variant showed significant changes in its intrinsic properties, while the T126I ACTC variant displayed a decrease in calcium sensitivity. This research contributes to the understanding on disease mechanism of these ACTC variants in the development of cardiomyopathy.