Strain in the leading head (red) drives myosin forward.

The longest journey may begin with a single step, but, in the case of myosin motor proteins moving along actin filaments, the start of the walking stride has been nearly impossible to observe. Now Burgess et al., reporting on page 983, reveal the prepower stroke conformation of myosin on actin, clearing a major hurdle to understanding myosin activity.

Previous work on myosin has focused primarily on myosin II, which has the unfortunate habit of dissociating from actin in the presence of ATP, making its prepower stroke conformation all but impossible to observe. As motor domains are highly conserved among different myosins, Burgess et al. looked at myosin V, a highly processive motor that drives mRNA, vesicle, and membrane trafficking. By combining electron microscope images of myosin V with crystallographic data from myosin II heads, the...

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