Myosin VI is a molecular motor involved in intracellular vesicle and organe
lle transport. To carry out its cellular functions myosin VI moves toward t
he pointed end of actin, backward in relation to all other characterized my
osins. Myosin V, a motor that moves toward the barbed end of actin, is proc
essive, undergoing multiple catalytic cycles and mechanical advances before
it releases from actin. Here we show that myosin VI is also processive by
using single molecule motility and optical trapping experiments. Remarkably
, myosin VI takes much larger steps than expected, based on a simple lever-
arm mechanism, for a myosin with only one light chain in the lever-arm doma
in. Unlike other characterized myosins, myosin VI stepping is highly irregu
lar with a broad distribution of step sizes.