FIGURE 4. A model for kinesin motility.

a, At high ATP concentrations, hydrolysis and phosphate release leading to trailing-head dissociation is rate-limiting (larger arrows represent slower steps). Once released, the trailing head is rapidly translated forwards by ATP isomerization-induced neck-linker docking in the partner head (indicated by ATP*), resulting in a rapid 8-nm step and a new two-head-bound intermediate. b, At low ATP concentrations, phosphate release occurs before the leading head binds an ATP molecule, producing a one-head-bound state in which the detached head is positioned behind the bound partner head. Although this head may interact transiently with the rear tubulin-binding site, we postulate that the conformation of the neck linker in this head is not compatible with ADP release and strong microtubule binding. Once ATP has bound to the forward head, the detached head translates forwards and, after a diffusional search, binds to a new tubulin subunit. ADP release from this head is now permitted by the backward-extending conformation of the neck linker in this two-head-bound state^{12, 22, 23, 28}.