Tropomyosin is a rod-shaped molecule composed of two intertwined polypeptides with a length approximately equal to that of seven actin molecules. Chains of tropomyosin molecules are arranged end to end along the actin thin filament. These tropomyosin molecules partially cover the myosin-binding site on each actin molecule, thereby preventing the cross-bridges from making contact with actin. Each tropomyosin molecule is held in this blocking position by troponin, a smaller, globular protein that is bound to both tropomyosin and actin. One molecule of troponin binds to each molecule of tropomyosin and regulates the access to myosin-binding sites on the seven actin molecules in contact with tropomyosin. This is the status of a resting muscle fiber; troponin and tropomyosin cooperatively block the interaction of cross-bridges with the thin filament.
To enable cross-bridges to bind to actin and begin cycling, tropomyosin molecules must be moved away from their blocking positions on actin. This happens when calcium binds to specific binding sites on troponin (not tropomyosin). The binding of calcium produces a change in the shape of troponin, which through troponin’s linkage to tropomyosin, drags tropomyosin away from the myosin-binding site on each actin molecule. Conversely, removal of calcium from troponin reverses the process, turning off contractile activity. Thus, cytosolic calcium-ion concentration determines the number of troponin sites occupied by calcium, which in turn determines the number of actin sites available for cross-bridge binding. Changes in cytosolic calcium concentration are controlled by electrical events in the muscle plasma membrane.