The first sight of the structure of muscle's power stroke is shown in this figure, taken from a paper by Carolyn Cohen and colleagues published on 4 September (Cell 94, 559-571; 1998). The authors report the crystallographic structure, at around 3 Å resolution, of the motor domain (MD) of myosin from the thick filaments of smooth (chicken gizzard) muscle in complex with its essential light chain (ELC). This complex (MDE) forms the main part of the myosin head, which converts chemical to mechanical energy via a conformational change induced by the hydrolysis of ATP (catalysed by actin in the thin filaments). Understanding the mechanism by which myosin (and other motor proteins) converts chemical to mechanical force — manifested as sliding between the thick and thin filaments of muscle fibres — is a long-sought goal, and the new data provide an exciting glimpse of the structural basis of this mechanism.

The tail of the myosin head contains a very long α-helical region, thought to be a ‘lever arm’ that rotates when ATP binds and is hydrolysed — this rotation is the basis of the power stroke. The crystallographic structure of the end of the power stroke has been described previously, and there have been indications that there is a swinging lever arm. But until the new results of Cohen and colleagues, which show the beginning of the power stroke, there has been no unequivocal structural evidence for this hypothesis.

The figure consists of two superimposed structures. The motor domain of myosin is in yellow, and the magenta and pink regions of the molecule are the lever arm. The bottom structure represents the end of the power stroke, in which the molecule is free of bound nucleotide. The top structure represents the beginning of the power stroke, in which an ATP analogue is bound to the myosin. In this structure, the light-blue region of the molecule is a model, necessary because the construct used lacks a regulatory light chain (RLC). The angle between the ends of the two lever-arm conformations is about 70°, which would produce a filament displacement of about 10 Å. This distance is consistent with measurements obtained from functional studies of muscle fibres, and from in vitro motility assays of the component proteins.

figure 1

Figure 1