The myosin motor

Smooth and skeletal muscle myosins have important functional differences with respect to their motor activities and their regulation. The differences in motor properties are evident in the behavior of smooth and skeletal muscle myosins in an in vitro motifity assay. Purified smooth muscle myosin propels actin filaments at one tenth the velocity of skeletal muscle myosin and produces an average of 3-4 times more force per unit time period than skeletal muscle myosin, as measured by a micro-needle assay (Warshaw et al 1990, Van Buren et al 1994). These differences in the functional properties of smooth and skeletal muscle myosins at the molecular level parallel differences in the functional properties of smooth and skeletal muscle tissues. Smooth muscle tissues produce the same isometric force per cross-sectional area as skeletal muscle, but contain only one fifth as much myosin (Murphy et al 1974). In addition, the maximal shortening velocities of smooth muscle tissues are 1-2 orders of magnitude slower than those of skeletal muscles (Murphy et al 1997). 

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Kinesins and other molecular motors. Before considering further how the myosin motor may work, we should look briefly at the kinesins, a different group of motor molecules,1683 which transport various cellular materials along microtubule "rails." They also participate in organization of the mitotic spindle and other microtubule-dependent activities.168a/b/C See Section C,2 for further discussion. More than 90 members of the family have been identified. Kinesin heads have much shorter necks than do the myosin heads. 

The details of the events are worth setting out for what they reveal about the nature of the conformational changes within the myosin motor... 

Uyeda, T. Q., Abramson, P. D., and Spudich, J. A. (1996). The neck region of the myosin motor domain acts as a lever arm to generate movement. Proc. Natl. Acad. Sri. USA 93, 4459-4464. 

Takizawa, P. A., and R. D. Vale. 2000. The myosin motor, Myo4p, binds Ashl mRNA via the adapter protein, She3p. Proc. Nat l. Acad. Sci. USA 97 5273-5278. 

Sata M, Matsuura M, Ikebe M (1996) Characterization of the motor and enzymatic properties of smooth muscle long SI and short HMM role of the two-headed structure on the activity and regulation of the myosin motor. Biochem 35 1111311118... 

Mechanochemical Coupling in Molecular Motors Insights from Molecular Simulations of the Myosin Motor Domain... 

A detailed molecular and mode analysis such as that performed for the myosin motors [79-81] is expected to provide further information on the coupling and strain between the two motor heads. 

Yu, H. B., Ma, L., Yang, Y., and Cui, Q. (2007) Meehanochemieal eoupling in the myosin motor domain. I. Insights from equilibrium aetive-site simulations, Plos Comput. Biol. 3, 199-213. 

The myosin motor is an ATPase, because it is driven by cyclic ATP binding to cause detachment, splitting to form ADP and Pi, and the sequential release initially of Pi with contraction and then of ADP in readiness for a new ATP to bind. The organism Dictostelium discoidium provides a convenient motor domain for studying muscle contraction because of its near identity to the myosin motor of skeletal muscle. 

Figure 1.5. The waters of Thales of the myosin II motor. Stereo views of the crystal structure of the myosin motor domain of Dictostelium discoidium in presence of ATP are shown. A Space-filling display showing water molecules on a sculptured surface of the myosin II motor. B Those water molecules throughout the entire structure that are sufficiently fixed in space to be seen by X-ray diffraction are...

Especially when seen in three dimensions, as in Figure 1.5 A, the stereo view of the myosin motor domain has the appearance of a sculpted surface. The surface contains crevices and depressions, as though formed from sandstone that had been weathered by wind and rain. Only a relatively few water molecules are seen in these surface recesses, because the majority of water molecules are too mobile to be observed by X-ray diffraction. Yet these surface crevices and depressions can be filled with water molecules that, by the consilient mechanism, contribute to the energy considerations of motor function. In this regard, it should be appreciated that only 10% to 20% of the existing water molecules are sufficiently fixed in space to be located by X-ray diffraction. ... 

When the space-filling protein component is removed, it becomes possible to view the located water molecules within the myosin motor. As shown in Figure 1.5B, an impressive number and distribution of the detected water molecules appear. It can also be expected that there are many more water molecules relevant to function of the myosin motor that are too mobile to be seen by X-ray diffraction, just as is apparent in the crevices and recesses of the surface. By the consilient mechanism these water molecules (seen in Fig. 1.5B and the additional unseen water molecules) are essential to motor function. These water molecules, which in our view are essential for Life, we choose to call the waters of Thales. Thus, as required for this protein motor to function by the consilient mechanism, internal water molecules do exist. Accordingly, in our view, this fundamental protein motor that produces motion contains ample water as part of the structure in order to function in the competition for water between oil-like and vinegar-like groups, which competition expresses as a repulsion between these groups. 

A dynamic change of the surface hydrophobicity of the myosin motor domain during the ATP hydrolysis... 

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