Fig. 3: HCM mutations Y115H and E497D alter human β-cardiac myosin sS1 single molecule biomechanics and ensemble properties.
The mean values ± SEM of a actin-detachment rates at zero load (k0), b force sensitivity (δ), and c stroke-size of single molecules of WT (n = 14 molecules from 2 independent protein preparations), Y115H (n = 12 molecules from 2 independent protein preparations) and E497D (n = 14 molecules from 2 independent protein preparations) β-cardiac myosin sS1 are plotted. A two-sample, two-sided unequal variance t-test (Welch’s t test) was used to compare WT and each mutant. n.s. indicates p > 0.05, *** indicates p ≤ 0.001, **** indicates p ≤ 0.0001. All numbers including exact p-values from multiple pairwise comparisons shown here are given in Supplementary Table 1. HCM mutations Y115H and E497D alter the duty-ratio, average force production, and average power production of β-cardiac myosin sS1 in opposite ways. The d duty ratios (Eq. (2)), e average force (Eq. (3)), and f average power outputs (Eq. (4)) are calculated for the resistive force-range for WT, Y115H, and E497D constructs from the measured values of detachment rate k0, actin-activated ATPase rate kcat, force-dependent detachment rate kdet(F), and stroke size (d). Curves for WT are shown in black, Y115H in red, and E497D in blue. Source data are provided as a Source Data file.
