Molecular mechanism of ATP-dependent actin-myosin interaction in muscle contraction

Among a variety of energy transduction mechanisms in biological systems, the mechanism of chemo-mechanical energy conversion in muscle contraction has been studied most intensively. From the standpoint of muscle biochemistry, muscle contraction is essentially the actomyosin ATPase reaction in solution. From the standpoint of muscle physiology, on the other hand, muscle contraction is the relative sliding between the thick and thin filaments resulting from the attachment-detachment cycle between actin and myosin. Although the large gap between muscle physiology and muscle biochemistry is now being gradually eliminated by various new experimental techniques such as the flash photolysis of caged compounds and in vitro motility assay systems, there still remain a number of uncertainties concerning the molecular mechanism of actin-myosin interaction coupled with hydrolysis of ATP. As described in this article, attention of most investigators in this research field has been focused on the detection of myosin head rotation coupled with muscle force generation. Unfortunately, however, attempts to detect the myosin head rotation have not yet been successful, despite the efforts of many investigators with various techniques including X-ray diffraction, quick freezing, and use of various probes attached to the myosin head. It seems therefore possible that the mechanism of muscle contraction might be different from the mechanism which have been generally accepted. This possibility seems to be supported, for example, by the unexpected dissociation between the ATPase activity and the force development in muscle fibers treated with anti-S-2 antibody (Fig. 9C).