Figure 3. The dual functions of myosin VI are regulated by load in vivo.

a) Dependence of dwell time on load under physiological 1.5 mM ATP and 100 µM ADP (data used in regression: blue points; model: blue curve). The model correctly predicts dwell times at higher forces (red). Within each condition, each data point represents a different myosin VI molecule. Cartoons depict myosin VI motors stepping along actin while attached via adapter proteins (grey ovals) to a membrane. At low loads, the rate of ADP binding (red arrow) is low (leftmost cartoon). The rear head predominantly binds ATP (green arrow), resulting in 2–3 steps s⁻¹. At moderate forces ADP competes with ATP for binding to the rear head, slowing the motor to less than 1 step s⁻¹ (center). At forces greater than ~2.5 pN, the stepping rate decreases rapidly as ADP out-competes ATP for binding (right). The motor takes slow backsteps before detaching from actin (see Supplemental Information). In this way, M6 is able to maintain tension at ~2 pN and relieve forces greater than ~2.5 pN.