Cardiac myosin heavy chain (MYH7) (MYH7)

Cardiac myosin heavy chain (MYH7) is the fundamental motor protein of the cardiac sarcomere, primarily expressed in the ventricles [UniProt P12883]. It functions as an ATPase that converts chemical energy into mechanical work, driving the sliding of thick and thin filaments during muscle contraction [PubMed: 29438114]. The C-zone of the thick filament is a critical regulatory region where MYH7 interacts with cardiac myosin-binding protein C (cMyBP-C) to maintain a super-relaxed state (SRX), characterized by very low ATP consumption and sequestered myosin heads [PubMed: 31524110]. Mutations in MYH7 or disruptions in this regulatory zone are central to the pathogenesis of hypertrophic cardiomyopathy (HCM), leading to hypercontractility and diastolic dysfunction [PubMed: 32493630]. Modern therapeutic strategies involve small-molecule modulators like mavacamten, which bind to MYH7 to stabilize the SRX state and reduce the number of active cross-bridges [FDA: Camzyos Label]. This targeted approach helps normalize cardiac output and reduce the left ventricular outflow tract obstruction seen in HCM patients [PubMed: 32931332].

Other names

Beta-myosin heavy chainMyosin-7Cardiac muscle beta myosin heavy chainMYH7Slow-twitch skeletal muscle myosin heavy chain

Modulation of the myosin ATPase cycle; cardiac myosin inhibitors (e.g., mavacamten) stabilize the super-relaxed state (SRX) and reduce the number of myosin heads available for cross-bridge formation, while cardiac myosin activators (e.g., omecamtiv mecarbil) increase the rate of phosphate release to enhance force production [PubMed: 32493630, PubMed: 21330487].