A Model for Caldesmon in Latch-Bridge Formation in Smooth Muscle

Abstract

The primary mechanism of regulation of smooth muscle contraction involves the Ca⁺-dependent and reversible phosphorylation of myosin¹. Stimulation of the smooth muscle cell leads to an elevation of cytosolic free Ca²⁺ concentration whereupon Ca²⁺ binds to calmodulin. Formation of the Ca²⁺-calmodulin complex is accompanied by a conformational change in the Ca²⁺-binding protein which is then capable of interaction with a target enzyme, in this case myosin light chain kinase (MLCK). The binding of calmodulin converts the kinase from the inactive apoenzyme form found in the resting cell to the active Ca²⁺-calmodulin-MLCK ternary complex. The active kinase catalyzes transfer of the terminal phosphoryl group of ATP to serine-19 on each of the two 20 kDa light chains of myosin. In the phosphorylated state, the MgATPase activity of myosin is substantially enhanced by actin. This biochemical parameter is thought to reflect a cross-bridge cycling mechanism whereby actin and myosin filaments slide relative to one another, the required energy being provided by the hydrolysis of ATP. At the level of the intact cell this process would result in force development.