Evidence for the Essential Role of Myosin Subfragment-2 in Muscle Contraction: Functional Communication between Myosin Head and Subfragment-2

In 1971, Harrington et al. put forward a hypothesis, in which helix-coil transition in the hinge region of myosin subfragment-2 (S-2) contributes to muscle contraction. The helix-coil transition hypothesis has been, however, ignored by muscle investigators over many years. In 1992, we worked with him to examine the effect of polyclonal antibody to myosin subfragment-2 (anti-S-2 antibody), and found that the antibody eliminated Ca2+-activated isometric force generation of skinned vertebrate muscle fibers without affecting MgATPase activity. Further studies using the same antibody indicated functional communication between myosin head and myosin S-2, including regulation of binding strength between myosin head and actin filament during Ca2+-activated contraction in vertebrate muscle fibers. These findings indicate that the swinging lever arm hypothesis, in which muscle contraction results from active rotation of myosin head converter domain, is incomplete because it ignores of the role of myosin S-2. Much more experimental work is necessary to reach full understanding of muscle contraction mechanism at the molecular level.