Rigor to post-rigor transition in myosin V: link between the dynamics and the supporting architecture

The detachment kinetics from actin upon ATP binding is a key step in the reaction cycle of myosin V. We show that a network of residues, constituting the allostery wiring diagram (AWD), that trigger the rigor (R) to post-rigor (PR) transition, span key structural elements from the ATP and actin-binding regions. Several of the residues are in the 33 residue helix (H18), P loop, and switch I. Brownian dynamics simulations show that a hierarchy of kinetically controlled local structural changes leads to the opening of the "cleft" region, resulting in the detachment of the motor domain from actin. Movements in switch I and P loop facilitate changes in the rest of the motor domain, in particular the rotation of H18, whose stiffness within the motor domain is crucial in the R --> PR transition. The finding that residues in the AWD also drive the kinetics of the R --> PR transition shows how the myosin architecture regulates the allosteric movements during the reaction cycle.