Skeletal muscle myosin heavy chain (MyHC) (MyHC)

Skeletal muscle myosin heavy chain (MyHC) is a critical motor protein that forms the backbone of the thick filament in striated muscle fibers. It functions as an ATPase, converting chemical energy from ATP into mechanical force through its interaction with actin filaments, a process fundamental to muscle contraction and locomotion (UniProt: P12883). In humans, multiple isoforms exist, including MYH7 (slow-twitch/cardiac), MYH2, MYH1, and MYH4 (fast-twitch), each dictating the contractile properties of the muscle fiber (PubMed: 21502330). Mutations in MyHC genes are linked to various congenital myopathies and distal arthrogryposis, while age-related declines in MyHC expression contribute to sarcopenia (NIH: GeneReviews). Therapeutically, MyHC is targeted by small molecule modulators; for instance, cardiac myosin inhibitors like Mavacamten are used for hypertrophic cardiomyopathy, while skeletal-specific activators are being investigated to improve physical function in neuromuscular diseases like ALS (PubMed: 28855244, FDA Label: Camzyos). These drugs typically bind to the myosin head or the "mesa" region to alter the duty cycle or the number of active cross-bridges (PubMed: 31548315).

Other names

Myosin heavy chainSkMHCMHCStriated muscle myosin heavy chainMyosin-1Myosin-2Myosin-4Myosin-7

Direct modulation of the myosin motor domain to either increase (activators) or decrease (inhibitors) the rate of ATP hydrolysis and the transition of myosin into the force-generating state.