FIGURE 1.

Schematic representation of the kinesin chemomechanical cycle that illustrates key transitions that influence processivity. A processive run is started by binding of either head followed by rapid ADP release to form the E1 intermediate where the leading head that forms the initial contact is microtubule-bound but nucleotide-free (Ø), whereas the trailing head is detached with ADP tightly bound. ATP binding to the leading head induces a series of structural transitions, including neck-linker docking that allows the trailing ADP-head to move 16 nm ahead to its new microtubule-binding site (E2–E4). ADP release from the new leading head (E4 and E5) results in the E5 two-head bound state, thereby generating intermolecular strain, which inhibits ATP binding at the now leading head. ATP hydrolysis at the trailing head followed by phosphate (P_i) release generates a microtubule weakly bound ADP state (E6 and E7). Detachment of the trailing head relieves the intermolecular strain (E7), and initiates the next motor cycle.