Problem 16

Background and context

Myosin II unfolds, assembles into active bipolar filaments, and becomes active to generate contraction when the regulatory LC is phosphorylated by the enzyme myosin light-chain kinase (MLC kinase), whose activity is regulated by the level of cytosolic free Ca²⁺.Calmodulin, a Ca²⁺-binding protein, is involved in the Ca²⁺-dependent regulation of MLC kinase activity. Calcium binds to calmodulin, causing the protein to alter shape, and the Ca²⁺ /calmodulin complex subsequently binds to MLC kinase, activating it. MLC kinase becomes inactive when Ca²⁺ returns to its resting level, and myosin light-chain phosphatase eliminates the phosphates, allowing the system to return to its relaxed state.

Because this mechanism of control relies on Ca²⁺ diffusion over longer distances than sarcomeres and the action of protein kinases, smooth muscle contractions are significantly slower than skeletal muscle contractions. Thick-filament regulation is named from the fact that it involves myosin.