Myosin is the most abundant protein in muscle fibrils, responsible for the elastic and contractile properties of muscle. It combines with actin to form actomyosin.
A viscous protein was extracted from muscle with concentrated salt solution by Kühne (1864), who called it “myosin” and considered it responsible for the rigor state of muscle1. Muralt and Edsall (1930) showed that the “myosin” in solution had a strong flow birefringence with indications that the particles were uniform in size and shape2. In 1935, Weber (1935) developed a new technique for the in vitro study of contraction. He squirted “myosin” dissolved in high salt into water where it formed threads that became strongly birefringent upon drying 3.
Myosin is a large asymmetric molecule; it has a long tail and two globular heads. The tail is about 1,600 Å long and 20 Å wide. Each head is about 165 Å long, 65 Å wide and 40 Å deep at its thickest part. The molecular weight of myosin is about 500kDa. In strong denaturing solutions, such as 5M guanidine-HCl or 8M urea, myosin dissociates into six polypeptide chains: two heavy chains (molecular weight of each heavy chain about 200 kDa) and four light chains (two with a molecular weight of 20 kDa, one with 15 kDa and another with 25 kDa). The two heavy chains are wound around each other to form a double helical structure. At one end both chains are folded into separate globular structures to form the two heads. In the muscle, the long tail portion forms the backbone of the thick filament and the heads protrude as cross bridges toward the thin filament. Each head contains two light chains. At low ionic strength, e.g. 0.03M KCl, myosin precipitates and forms myosin filaments. Electron micrographs reveal the specific structure of the filaments that is their central shaft and side projections. Myofibrils are tiny muscle fibers, prepared by homogenization of freshly dissected muscle in physiological salt solution. Myofibrils contain the contractile (myosin and actin) and the regulatory proteins (tropomyosin and troponin) of muscle.
Mode of Action
Muscles generate force and shortening in a cyclical interaction between the myosin head domains projecting from the myosin filaments and the adjacent actin filaments. Although many features of the dynamic performance of muscle are determined by the rates of attachment and detachment of myosin and actin, the primary event in force generation is thought to be a conformational change or 'working stroke' in the actin-bound myosin head 4. In the absence of calcium ions, tropomyosin blocks access to the myosin binding site of actin. When calcium binds to troponin, the positions of troponin and tropomyosin are altered on the thin filament and myosin then has access to its binding site on actin. Myosin hydrolyzes ATP and undergoes a conformational change into a high-energy state. The head group of myosin binds to actin forming a cross-bridge between the thick and thin filaments. The energy stored by myosin is released, and ADP and inorganic phosphate dissociate from myosin. The resulting relaxation of the myosin molecule entails rotation of the globular head, which induces longitudinal sliding of the filaments. When the calcium level decreases, troponin locks tropomyosin in the blocking position and the thin filament slides back to the resting state 5.
Myosin has multiple functions - Filament formation, ATPase activity, and reversible combination with actin. The use of proteolytic enzymes revealed different regions of the myosin molecule were responsible for each of these different functions.
Myosin-actin binding - One of the biologically important properties of myosin is its ability to combine with actin. The complex formed is called actomyosin. The actin binding by myosin is highly specific; no other protein can substitute actin. Physiologically, when actin and myosin combine the muscle produces force. There are several methods to measure the stoichiometry of actin to myosin combination.
ATPase activity of myosin - A Russian husband wife team, Engelhardt and Lyubimova, made the important discovery in 1939 that myosin is an enzyme that hydrolyzes ATP6. It was already known that ATP is the universal energy donor in living cells, thus Engelhardt and Lyubimova created the term mechanochemistry i.e. the contractile protein myosin that carries out the work also liberates the energy necessary for the work.
Myosin filament - At low ionic strength, e.g. 0.03M KCl, myosin precipitates and forms filaments. Since individual myosin molecules have a globular region at one end only, the filaments are formed by anti parallel association of myosin molecules. All the molecules in one half filaments are oriented in one direction and all those in the other half of the filaments are oriented in the opposite direction. Thus, in the middle of the filament the tails of antiparallel molecules overlap yielding a bare central shaft, and globular regions are projected at both ends of the filament7.
ATPase activity of myosin and speed of muscle shortening - The ATPase activity of myosin was determined in 25 different muscles with a 250-fold variation in the speed of shortening. A correlation was found between the ATPase activity of myosin and the speed of shortening. This suggests that the myosin ATPase determines the speed of muscle shortening 8.
1. Kühne, W. (1864). Untersuchungen über das Protoplasma und die Contractilitat. W. Engelmann, Leipzig.
2. Von Muralt, A. L., and Edsall, J. T. (1930). Studies in the physical chemistry of muscle globulin. J. Biol. Chem., 89:315 -350.
3. Weber, H.H. 1935. Der feinbau und die mechanischen eigenschaften des myosin-fadens. Arch. Physiol. 235:205–233.
4. Szent-Györgyi AG (2004). Early History of the Biochemistry of Muscle Contraction. J. Gen. Physiol., 123(6): 631–641.
5. Book : Neurobiology, molecules, cells and system By Gary G .Matthews.
6. Engelhardt, V.A., and M.N. Lyubimova (1939). Myosin and adenosinetriphosphatase. Nature., 144:668-669.
7. Hidalgo C, Padron R, Horowitz R, Zhao FG, Craig R (2001). Purification of native myosin filaments from muscle. Biophys. J., 81(5):2817-2826.
8. Bárány, M. (1967). ATPase activity of myosin correlated with speed of muscle shortening. J. Gen. Physiol., 50(6):197-218.
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