Figure 16–56 Kinesin and kinesinrelated proteins. Structures of four kinesin superfamily members. As in the myosin superfamily, only the motor domains are conserved. Kinesin-1 has the motor domain at the N-terminus of the heavy chain. The middle domain forms a long coiled-coil, mediating dimerization. The C-terminal domain forms a tail that attaches to cargo, such as a membrane-enclosed organelle. Kinesin-5 forms tetramers where two dimers associate by their tails. The bipolar kinesin-5 tetramer is able to slide two microtubules past each other, analogous to the activity of the bipolar thick filaments formed by myosin II. Kinesin-13 has its motor domain located in the middle of the heavy chain. It is a member of a family of kinesins that have lost typical motor activity and instead bind to microtubule ends to promote depolymerization (see Figure 16–52). Kinesin-14 is a C-terminal kinesin that includes the Drosophila protein Ncd and the yeast protein Kar3. These kinesins generally travel in the opposite direction from the majority of kinesins, toward the minus end instead of the plus end of a microtubule.
Figure 16–57 The mechanochemical cycle of kinesin. Kinesin-1 is a dimer of two nucleotide-binding motor domains (heads) that are connected through a long coiled-coil tail (see Figure 16–56). The two kinesin motor domains work in a coordinated manner; during a kinesin “step,” the rear head detaches from its tubulin binding site, passes the partner motor domain, and then rebinds to the next available tubulin binding site. Using this “handover-hand” motion, the kinesin dimer can move for long distances on the microtubule without completely letting go of its track.
At the start of each step, one of the two kinesin motor domain heads, the rear or lagging head (dark green), is tightly bound to the microtubule and to ATP, while the front or leading head is loosely bound to the microtubule with ADP in its binding site. The forward displacement of the rear motor domain is driven by the dissociation of ADP and binding of ATP in the leading head (between panels 2 and 3 in this drawing). The binding of ATP to this motor domain causes a small peptide called the “neck linker” to shift from a rearward-pointing to a forward-pointing conformation (the neck linker is drawn here as a purple connecting line between the leading motor domain and the intertwined coiled-coil). This shift pulls the rear head forward, once it has detached from the microtubule with ADP bound [detachment requires ATP hydrolysis and phosphate (Pi) release]. The kinesin molecule is now poised for the next step, which proceeds by an exact repeat of the process shown (Movie 16.9).
the protofilament to a binding site 8 nm closer to the microtubule plus end, which is the distance between tubulin dimers of a protofilament. The nucleotide-hydrolysis cycles in the two heads are closely coordinated, so that this cycle of linker docking and undocking allows the two-headed motor to move in a hand-overhand (or head-over-head) stepwise manner (Figure 16–57).