Kinesin Processivity

Conventional kinesin is a highly processive motor that can take Ͼ 100 steps along a microtubule before dissociating. Various lines of evidence have led to a model of hand over hand processive motion, in which the trailing head detaches and rebinds to the next open tubulin dimer site on the same protofilament, leading to an 8-nm movement of supports the hand over hand mechanism. Processivity is a competition between the detachment and rebinding of one head in order to take a step, and the rate of dissociation of the complex while only one head is bound. Although processivity is thought to require two heads in the case of conventional kinesin, a mono-meric kinesin construct of KIF1A is processive (Okada and Hirokawa, 1999). This surprising result has been explained by a diffusive motion within the electrostatic field of the microtubule, biased by some conformational change coupled to the ATPase cycle (Okada and Hirokawa, 2000). It is not clear how dimeric kinesin takes the step to the next binding site on tubulin. Important progress in identifying the structural change necessary for a step is reported in two papers in this issue (Thorn et al., 2000; Tomishige and Vale, 2000). In addition, the results point to an unexpected similarity in the mechanism of motion of conventional kinesin and KIF1A. The determination of the structure of the rat kinesin dimer bound to ADP (Kozielski et al. 1997) raised the question of whether the two heads could ever be simultaneously bound to successive tubulin dimer units. The orientation of kinesin in Fig. 1 corresponds to the position with the trailing head bound and the plus end of the micro-tubule pointing up. Based on docking the crystal structure to the electron micrograph, the coiled-coil segment (Fig. 1, green) is along the surface of the microtubule, perpendicular to the direction of motion (Hoenger et al., 1998; Rice et al., 1999). An alternative docking mechanism has been proposed in which the coiled-coil is pointing away from the microtubule and the second head is detached (Hirose et al., 1999). If we tentatively accept the first alternative, the orientation of the dimer in the figure is roughly as it would appear while walking along the microtubule surface from top to bottom. The trailing head is bound to the mi-crotubule and the leading head is free to rotate away from the previous microtubule binding site. However, the distance between heads is …