Actomyosin powers muscle contraction and various cellular activities including cell division, differentiation, intracellular transport and sensory functions. Despite their crucial roles, key aspects of force generation have remained elusive. To perform efficient force generation, the powerstroke must occur while myosin is bound to actin. Paradoxically, this process must be initiated when myosin is in a very low actin-affinity state. Recent results shed light on a kinetic pathway selection mechanism whereby the actin-induced activation of the swing of myosin's lever enables efficient mechanical functioning. Structural elements and biochemical principles involved in this mechanism are conserved among various NTPase-effector (e.g. kinesin-microtubule, G protein-exchange factor and kinase-scaffold protein) systems that perform chemomechanical or signal transduction.
Allosteric activation in motor and signaling systemsActomyosin is the best-understood of the ubiquitous mechanochemical systems of eukaryotic organisms [1,2]. The key action of the actomyosin mechanochemical cycle is the powerstroke, a rowing action of the myosin head which results from the swing of its lever (Box 1). To produce effective translocation along actin, the lever swing must occur with the myosin head in an actin-bound state (Fig. 1); the occurrence of a futile lever swing in an actin-detached state leads to an ATP-wasting cycle (Fig. 1). The powerstroke can be viewed as the result of three linked events: binding of the myosin head to actin, structural changes in the head leading to a strong actomyosin interaction, and the lever swing. These events lead to the release of ATP hydrolysis products, P i (inorganic phosphate) and ADP.
Box 1 Myosin structural elementsMyosin is a P-loop NTPase, and diverse isoforms of myosin are divided into at least 35 classes [5]. Myosin has three functional parts: the motor domain, the lever and the tail region (Fig. IA). The heavy chain subunit forms the motor domain, the axis of the lever, and the tail, whereas the light chains stabilize the structure of the lever. In some myosin classes, further light chains bind to the tail region. The tail generally confers effector functions and, in some classes, is responsible for heavy chain dimerization. In the myosin II class, which includes the muscle myosins, the tail is a long coiled-coil rod responsible for filament formation. The motor domain confers the mechanoenzymatic function of