Fast skeletal muscle myosin-2 (fsMyo2) (fsMyo2)

Fast skeletal muscle myosin-2 isoforms, primarily Myosin Heavy Chain 1 (MYH1), 2 (MYH2), and 4 (MYH4), are the fundamental motor proteins driving the contraction of fast-twitch (Type II) muscle fibers. These proteins function as ATP-dependent molecular motors that interact with actin filaments to generate force and movement through the cross-bridge cycle (UniProt: P12882, Q9UKX2). In various neuromuscular and chronic diseases, such as Amyotrophic Lateral Sclerosis (ALS), Spinal Muscular Atrophy (SMA), and sarcopenia, the loss of fast-twitch fiber function contributes significantly to muscle weakness and physical disability (PubMed: 28855244). Therapeutic strategies targeting these isoforms aim to enhance muscle contractility and power output by modulating the myosin motor's kinetics. Direct myosin activators, such as CK-2066260, increase the rate of the force-generating transition in the myosin cycle, thereby boosting muscle performance even at submaximal calcium levels (Cytokinetics, 2017). Conversely, selective inhibitors like N-benzyl-p-toluene sulfonamide (BTS) are utilized in research to dissect the specific mechanical contributions of fast-twitch fibers (PubMed: 12183387). While clinical development has largely focused on troponin activators, direct myosin modulation represents a potent approach for treating conditions characterized by impaired skeletal muscle function.

Other names

Fast skeletal muscle myosin heavy chainType II skeletal muscle myosinMYH1MYH2MYH4Myosin-1Myosin-2Myosin-4Fast-twitch skeletal muscle myosin

Direct activation of the myosin-actin cross-bridge cycle by accelerating the rate of phosphate release or increasing the transition rate to the force-generating state.