In a muscle at rest,
myosin is already primed for action. The myosin head has bound ATP in its catalytic core and cleaved it into ADP and phosphate (P i), which has wound the myosin head up like a spring. Preventing any further action however, is tropomyosin, which blocks the myosin binding sites on actin.
The tropomyosin barrier is held in place by troponin molecules
TnT, TnI, and TnC. When muscle contraction is signalled by the brain, calcium ions are released into the muscle. TnC senses this calcium and pulls TnI out of tropomyosin's way. Tropomyosin then moves into the spot vacated by TnI, exposing the myosin binding sites on actin.
Once the binding sites are uncovered by troponin/tropomyosin, myosin moves to bind to actin: first, myosin forms weak electrostatic interactions between its positively charged (
pink) and negatively charged ( cyan) residues on actin. Second, hydrophobic interactions ( yellow) ensure myosin locks onto actin correctly.
Binding actin opens the myosin catalytic pocket where
phosphate is held, releasing it. Phosphate release triggers myosin’s head to spring open, shoving actin past it in a “power stroke”. The cumulative effect of many myosin motors working together is the rapid sliding of the actin thin filament past the myosin thin filament.
After the power stroke, ADP becomes less tightly bound by the residues in myosin’s catalytic binding pocket and is able to escape. A new molecule of ATP rushes into the empty pocket.
ATP binding to the catalytic pocket causes a cleft to form in myosin at its actin-binding surface. This disrupts myosin interaction with actin and leads to rapid detachment of the myosin head from the actin molecule.
Once detached, myosin winds up like a spring, so it can position its catalytic residues to hydrolyze ATP into
ADP and phosphate ( P). Hydrolysis causes the actin binding surface to reform and myosin is now ready to bind another molecule of actin. i