External loads asymmetrically affect ADP affinity in myosins V and VI, with forward loads modestly accelerating and backward loads inhibiting ADP dissociation, generating an intramolecular load of ~2 pN.
Dimeric myosins V and VI travel long distances in opposite directions along actin filaments in cells, taking multiple steps in a "hand-over-hand" fashion. The catalytic cycles of both myosins are limited by ADP dissociation, which is considered a key step in the walking mechanism of these motors. Here, we demonstrate that external loads applied to individual actomyosin V or VI bonds asymmetrically affect ADP affinity, such that ADP binds weaker under loads assisting motility. Model-based analysis reveals that forward and backward loads modulate the kinetics of ADP binding to both myosins, although the effect is less pronounced for myosin VI. ADP dissociation is modestly accelerated by forward loads and inhibited by backward loads. Loads applied in either direction slow ADP binding to myosin V but accelerate binding to myosin VI. We calculate that the intramolecular load generated during processive stepping is approximately 2 pN for both myosin V and myosin VI. The distinct load dependence of ADP binding allows these motors to perform different cellular functions.
Oguchi et al. (Thu,) reported a other. External loads applied to individual actomyosin V or VI bonds was evaluated on ADP affinity and dissociation kinetics. External loads asymmetrically affect ADP affinity in myosins V and VI, with forward loads modestly accelerating and backward loads inhibiting ADP dissociation, generating an intramolecular load of ~2 pN.
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