Skeletal muscle myosin (SkM-Myosin) (SkM-Myosin)

Skeletal muscle myosin is a hexameric motor protein that serves as the primary molecular engine for voluntary movement in vertebrates. It belongs to the Myosin II (conventional myosin) family and is composed of two heavy chains (MYH) and four light chains (MYL). The heavy chains contain a globular head domain with ATPase activity and an actin-binding site, a neck region, and a long coiled-coil tail that facilitates filament assembly. During muscle contraction, myosin heads undergo a cyclic interaction with actin filaments—the cross-bridge cycle—driven by ATP hydrolysis, which generates the mechanical force required for muscle shortening [StatPearls: Muscle Contraction, 2023]. In humans, different isoforms of skeletal muscle myosin heavy chains (such as MYH1, MYH2, and MYH7) define the physiological properties of muscle fibers, including contraction speed and fatigue resistance [UniProt: P12883]. Mutations in these genes are linked to various congenital myopathies and distal arthrogryposis syndromes [PubMed: 21138942]. Pharmacologically, skeletal muscle myosin is an emerging therapeutic target for small molecules designed to modulate contractile performance. Direct myosin activators like CK-2066260 are being developed to enhance muscle power and function in patients with neuromuscular diseases such as Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA), while inhibitors are researched for conditions involving muscle spasticity [Cytokinetics; PubMed: 30104234].

Other names

Myosin-2Myosin IISarcomeric myosinMyosin heavy chain (MHC)Myosin light chain (MLC)Striated muscle myosin

Skeletal muscle myosin activators (e.g., CK-2066260) increase the rate of phosphate release from the myosin-ADP-Pi complex, accelerating the transition of myosin into the strongly bound, force-producing state with actin [Cytokinetics; PubMed: 30104234]. Conversely, inhibitors like BTS stabilize the low-affinity, non-force-generating state of the myosin head by blocking the ATPase cycle [PubMed: 12183387].