Fig. 7

Proposed model of myosin-5B regulation by force and Ca²⁺. a In the presence of assistive forces, myosin-5B moves in the direction of the force at full speed by consecutive steps towards the plus actin end. However, assistive forces drastically reduce myosin run length as a consequence of accelerated detachment of the motor from actin. On the other hand, resistive forces slow down the motor and reduce its run length as a consequence of increased back stepping. b (1) In the absence of Ca²⁺, myosin-5B folds in an enzymatically and mechanically inactive conformation where head-tail interaction hinders binding to actin. (2) As Ca²⁺ concentration increases, myosin-5B switches to an open conformation that can bind to actin, thus becoming enzymatically active. However, Ca²⁺-induced detachment of 25% of CaM molecules results in loss of myosin processivity. (3) In the presence of excess CaM (2–5 μM), new CaM molecules are available for occupying the vacant binding sites on the light chains, thus restoring myosin capability to move along actin