Figure 5. Force-dependent transport and anchoring mechanisms of myosin VI.

(a) Examples of myosin VI transport and anchor function in cells. Endocytic vesicle transport and the maintenance of stereocillia are shown as examples. (b) Hand-over-hand motion is used for transport, which occurs under low loads. Here, one head in a myosin VI dimer undergoes one 72 nm step per two successive ATP hydrolysis cycles³⁰, whereas the tail moves 20–40 nm per ATP hydrolysis cycle³². (c) Inchworm-like motion occurs at high loads. Here, one head undergoes 43 nm steps per one ATP hydrolysis cycle (states i and ii). In the adjacent binding state (state iii), either head can take the forward step with equal probability³⁴, which results in a synergistic lever arm swing (state v to vi) to produce 20–40 nm tail motion. At stall force, myosin VI remains at state iii, iv or v. Transitions from state iv to iii or v to iv should result from spontaneous detachment of the front head⁴⁹. Transitions from state iii to ii would be possible at over stall force (>2.5 pN), resulting in backward motion by the tail²².