Cartoon showing the proposed effect of cMyBP-C phosphorylation and ablation on myosin head position. (A) Unphosphorylated cMyBP-C interacting with myosin in the S2 coiled-coil, positioning myosin heads further away from the thin filament, thereby decreasing the probability of cross-bridge formation. (B) Maximally phosphorylated cMyBP-C in which interaction with S2 is abolished and myosin heads are positioned closer to the thin filament, thereby increasing the probability of cross-bridge formation. (C) In the absence of cMyBP-C (cMyBP-C^−/−), myosin heads are positioned closer to the thin filament, thereby increasing the probability of cross-bridge formation. Myosin is shown in blue, actin in tan, and cMyBP-C in green.