35.1 Most Molecular-Motor Proteins Are Members of the P-Loop NTPase Superfamily

Eukaryotic cells contain three families of molecular-motor proteins: myosins, kinesins, and dyneins. These proteins move along tracks defined by the actin and microtubule cytoskeletons of eukaryotic cells, contributing to cell and organismal movement and to the intracellular transport of proteins, vesicles, and organelles. Despite considerable differences in size and a lack of similarity detectable at the level of amino acid sequence, these proteins are homologous, containing core structures of the P-loop NTPase family. The ability of these core structures to change conformations in response to nucleoside triphosphate binding and hydrolysis is key to molecular-motor function. Motor proteins consist of motor domains attached to extended structures that serve to amplify the conformational changes in the core domains and to link the core domains to one another or to other structures.

35.2 Myosins Move Along Actin Filaments

The motile structure of muscle consists of a complex of myosin and actin, along with accessory proteins. Actin, a highly abundant 42-kDa protein, polymerizes to form long filaments. Each actin monomer can bind either ATP or ADP. A myosin motor domain moves along actin filaments in a cyclic manner, beginning with myosin free of bound nucleotides bound to actin: (1) ATP binds to myosin and the myosin is released from actin; (2) a reversible conformational change associated with the hydrolysis of ATP while still bound to myosin leads to a large motion of a lever arm that extends from the motor domain; (3) myosin with bound ADP and P_i binds to actin; (4) P_i is released from myosin, resulting in resetting the position of the lever arm and moving actin relative to myosin; and (5) the release of ADP returns the motor domain to its initial state. The length of the lever arm determines the size of the step taken along actin in each cycle. The ability to monitor single molecular-motor proteins has provided key tests for hypotheses concerning motor function. Muscle contraction entails the rapid sliding of thin filaments, composed of actin, relative to thick filaments, composed of myosin. The thick filaments consist of multiple myosin molecules bound together. Each myosin molecule has two heads that can bind to actin and move it relative to myosin, driven by the hydrolysis of ATP by myosin. Muscle contraction is regulated by tropomyosin and the troponin complex. These proteins prevent actin and myosin from productively interacting until an increase in calcium concentration associated with a nerve impulse results in calcium-induced changes in troponin and tropomyosin.

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35.3 Kinesin and Dynein Move Along Microtubules

Kinesin and dynein move along microtubules rather than actin. Microtubules are polymeric structures composed of α- and β-tubulin, two very similar guanine-nucleotide-binding proteins. Each microtubule comprises 13 protofilaments with alternating α- and β-tubulin subunits. Kinesins move along microtubules by a mechanism quite similar to that used by myosin to move along actin but with several important differences. First, ATP binding to kinesin favors motor-domain binding rather than dissociation. Second, the power stroke is triggered by the binding of ATP rather than the release of P_i. Finally, kinesin motion is processive. The two heads of a kinesin dimer work together, taking turns binding and releasing the microtubule, and many steps are taken along a microtubule before both heads dissociate. Most kinesins move toward the plus end of microtubules.

35.4 A Rotary Motor Drives Bacterial Motion

Many motile bacteria use rotating flagella to propel themselves. When rotating counterclockwise, multiple flagella on the surface of a bacterium come together to form a bundle that effectively propels the bacterium through solution. A proton gradient across the plasma membrane, rather than ATP hydrolysis, powers the flagellar motor. The mechanism for coupling transmembrane proton transport to macromolecular rotation appears to be similar to that used by ATP synthase. When rotating clockwise, the flagella fly apart and the bacterium tumbles. Bacteria swim preferentially toward chemoattractants in a process called chemotaxis. When bacteria are swimming in the direction of an increasing concentration of a chemoattractant, clockwise flagellar motion predominates and tumbling is suppressed, leading to a biased random walk in the direction of increasing chemoattractant concentration.