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activity, and, when anchored to a glass surface in vitro, these proteins, in the presence of ATP, can bind microtubules and move them through the solution. In the cell, cytosolic dyneins specifically move organelles and vesicles from the plus end of a microtubule to the minus end. Thus, as shown in Figure 17.8, dyneins move vesicles and organelles from the cell periphery toward the cen-trosome (or, in an axon, from the synaptic termini toward the cell body). The

Kinesin

Kinesin

Minus end

Plus end

FIGURE 17.8 • (a) Rapid axonal transport along microtubules permits the exchange of material between the synaptic terminal and the body of the nerve cell. (b) Vesicles, multivesicular bodies, and mitochondria are carried through the axon by this mechanism. (Adapted from a drawing by Ronald Vale)

Minus end

Plus end

FIGURE 17.8 • (a) Rapid axonal transport along microtubules permits the exchange of material between the synaptic terminal and the body of the nerve cell. (b) Vesicles, multivesicular bodies, and mitochondria are carried through the axon by this mechanism. (Adapted from a drawing by Ronald Vale)

kinesins, on the other hand, assist the movement of organelles and vesicles from the minus end to the plus end of microtubules, resulting in outward movement of organelles and vesicles. Kinesin is similar to cytosolic dyneins but smaller in size (360 kD), and contains subunits of 110 kD and 65 to 70 kD. Its length is 100 nm. Like dyneins, kinesins possess ATPase activity in their globular heads, and it is the free energy of ATP hydrolysis that drives the movement of vesicles along the microtubules.

The N-terminal domain of the kinesin heavy chain (38 kD, approximately 340 residues) contains the ATP- and microtubule-binding sites and is the domain responsible for movement. Electron microscopy and image analysis of tubulin-kinesin complexes reveals (Figure 17.9) that the kinesin head domain is compact and primarily contacts a single tubulin subunit on a microtubule surface, inducing a conformational change in the tubulin subunit. Optical trapping experiments (see page 554) demonstrate that kinesin heads move in 8-nm (80-A) steps along the long axis of a microtubule. Kenneth Johnson and his coworkers have shown that the ability of a single kinesin tetramer to move unidirectionally for long distances on a microtubule depends upon cooperative interactions between the two mechanochemical head domains of the protein.

FIGURE 17.9 • The structure of the tubulin-kinesin complex, as revealed by image analysis of cryoelectron microscopy data. (a) The computed, three-dimensional map of a microtubule, (b) the kinesin globular head domain-microtubule complex, (c) a contour plot of a horizontal section of the kinesin-microtubule complex, and (d) a contour plot of a vertical section of the same complex. (Taken from Kikkawa et al, 1995. Nature 376:274—277. Photo courtesy of Nobutaka Hirokawa.)

FIGURE 17.9 • The structure of the tubulin-kinesin complex, as revealed by image analysis of cryoelectron microscopy data. (a) The computed, three-dimensional map of a microtubule, (b) the kinesin globular head domain-microtubule complex, (c) a contour plot of a horizontal section of the kinesin-microtubule complex, and (d) a contour plot of a vertical section of the same complex. (Taken from Kikkawa et al, 1995. Nature 376:274—277. Photo courtesy of Nobutaka Hirokawa.)

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