Dissecting the Kinematics of the Kinesin Step

Abstract

Kinesin walks processively on microtubules in an asymmetric hand-over-hand manner with each step spanning 16 nm. We used molecular simulations to determine the fraction of a single step due to conformational changes in the neck linker, and that due to diffusion of the tethered head. Stepping is determined largely by two energy scales, one favoring neck-linker docking and the other, ε(h)(MT-TH), between the trailing head (TH) and the microtubule. Neck-linker docking and an optimal value of ε(h)(MT-TH) are needed to minimize the probability that the TH takes side steps. There are three major stages in the kinematics of a step. In the first, the neck linker docks, resulting in ∼(5-6) nm movements of the trailing head. The TH moves an additional (6-8) nm in stage II by anisotropic translational diffusion. In the third stage, spanning ∼(3-4) nm, the step is complete with the TH binding to the αβ-tubulin binding site.