Myosin mutants in the optical trap

Hypertrophic cardiomyopathy (HCM) is a symptomatic affliction due to mutations in cardiac contractile proteins. We compared a highly penetrant mutation in cardiac myosin, M493I, with wild type (WT) using an advanced optical trap assay capable of quantifying kinetic rates including actomyosin re-attachment. Kinetic changes in both the actomyosin attachment and detachment rates suggest that the equilibrium between a conformation termed the Interacting Head Motif (IHM) and freely available myosin heads is disturbed in M493I. This type of disruption has been hypothesized to lead to the toxic hypertrophy observed in patients.