Given here is a model of an actin-myosin complex with skeletal myosin S1 (heavy chain, blue; ELC, green) in a strongly bound S state (lever arm down, postpowerstroke) on F-actin (gray). Spheres show the labeling sites on actin (C374, gray) and on myosin ELC (C16, green), and the HCM mutation (E56G, yellow). Not shown is the weakly bound W state (prepowerstroke), in which the ELC-containing lever arm is tilted up. The FRET sensor (donor at actin 374, acceptor at ELC C16) was designed to determine the effect of the E56G HCM mutation in hVELC on the W-to-S structural transition in cardiac actomyosin. The model structure was adapted from Aydt et al. (62). To see this figure in color, go online.