Myosin VI is an actin-based motor that moves backwards

Myosins and kinesins are molecular motors that hydrolyse ATP to track along actin filaments and microtubules, respectively. Although the kinesin famil y includes motors that move towards either the plus or minus ends of microt ubules(1), all characterized myosin motors move towards the barbed (+) end of actin filaments(2). Crystal structures of myosin II (refs 3-6) have show n that small movements within the myosin motor core are transmitted through the 'converter domain' to a 'lever arm' consisting of a light-chain-bindin g helix and associated light chains(5,6), The lever arm further amplifies t he motions of the converter domain into large directed movements(3,5-7). He re we report that myosin VI, an unconventional myosin(8-12), moves towards the pointed (-) end of actin. We visualized the myosin VI construct bound t o actin using cryo-electron microscopy and image analysis, and found that a n ADP-mediated conformational change in the domain distal to the motor, a s tructure likely to be the effective lever arm, is in the opposite direction to that observed for other myosins, Thus, it appears that myosin VI achiev es reverse-direction movement by rotating its lever arm in the opposite dir ection to conventional myosin lever arm movement.