Figure 16–27 The myosin II bipolar thick filament in muscle. (A) Electron micrograph of a myosin II thick filament isolated from frog muscle. Note the central bare zone, which is free of head domains. (B) Schematic diagram, not drawn to scale. The myosin II molecules aggregate by means of their tail regions, with their heads projecting to the outside of the filament. The bare zone in the center of the filament consists entirely of myosin II tails. (C) A small section of a myosin II filament as reconstructed from electron micrographs. An individual myosin molecule is highlighted in green. The cytoplasmic myosin II filaments in non-muscle cells are much smaller, although similarly organized (see Figure 16–39). (A, courtesy of Murray Stewart; C, based on R.A. Crowther, R. Padrón and R. Craig, J. Mol. Biol. 184:429–439, 1985. With permission from Academic Press.)
Each myosin head binds and hydrolyzes ATP, using the energy of ATP hydrolysis to walk toward the plus end of an actin filament (Figure 16–28). The opposing orientation of the heads in the thick filament makes the filament efficient at sliding pairs of oppositely oriented actin filaments toward each other, shortening the muscle. In skeletal muscle, in which carefully arranged actin filaments are aligned in “thin filament” arrays surrounding the myosin thick filaments, the ATP-driven sliding of actin filaments results in a powerful contraction. Cardiac and smooth muscle contain myosin II molecules that are similarly arranged, although different genes encode them.
Myosin Generates Force by Coupling ATP Hydrolysis to Conformational Changes
Motor proteins use structural changes in their ATP-binding sites to produce cyclic interactions with a cytoskeletal filament. Each cycle of ATP binding, hydrolysis, and release propels them forward in a single direction to a new binding site along the filament. For myosin II, each step of the movement along actin is generated by the swinging of an 8.5-nm-long α helix, or lever arm, which is structurally stabilized by the binding of light chains. At the base of this lever arm next to the head, there is a pistonlike helix that connects movements at the ATP-binding cleft in the head to small rotations of the so-called converter domain. A small change at this point can swing the helix like a long lever, causing the far end of the helix to move by about 5.0 nm.
These changes in the conformation of the myosin are coupled to changes in its binding affinity for actin, allowing the myosin head to release its grip on the actin filament at one point and snatch hold of it again at another. The full mechanochemical cycle of nucleotide binding, nucleotide hydrolysis, and phosphate release (which causes the “power stroke”) produces a single step of movement (Figure 16–29). At low ATP concentrations, the interval between the force-producing step and the binding of the next ATP is long enough that single steps can be observed (Figure 16–30).
Sliding of Myosin II Along Actin Filaments Causes Muscles to Contract
Muscle contraction is the most familiar and best-understood form of movement in animals. In vertebrates, running, walking, swimming, and flying all depend on the rapid contraction of skeletal muscle on its scaffolding of bone, while involuntary