Structure and catalytic cycle of the kinesin motor domain.

<p>(<b>A</b>) The motor domain is composed of an eight-stranded antiparallel β-sheet surrounded by three major helices on either side. The ATPase catalytic site sits at the top of the β-sheet and is flanked by highly conserved loops, the P-loop (red), SI (blue) and SII (orange), which connect to helices on either side of the central sheet (α2, α3 and α4 respectively). The microtubule-binding interface has been mapped by Alanine scanning mutagenesis and limited proteolysis to the opposite side of the motor domain (green, encompassing the loop11, α4, loop12 and loop8 regions). Adjacent to the motor domain is the neck linker (purple), a flexible region that has been shown to undergo a nucleotide-dependent transition from a disordered to an ordered structure. Loop7 (yellow) and the motor domain tip are also indicated. (<b>B</b>) Motor domain secondary structure topology. β-strands are depicted as triangles and α-helices as circles. Regions are colored as in panel <b>A</b>. (<b>C</b>) Kinesin catalytic cycle. Kinesin (K) has a weak affinity for the microtubule (MT) in the ADP-state. ADP release, which is promoted by MT binding, is followed by strong binding to the MT. Subsequently, ATP binding may occur followed by hydrolysis and product release to regenerate the weakly bound ADP state.