Plus and minus ends of microtubules respond asymmetrically to kinesin binding by a long-range directionally driven allosteric mechanism.

Although it is known that majority of kinesin motors walk predominantly toward the plus end of microtubules (MTs) in a hand-over-hand manner, the structural origin of the stepping directionality is not understood. To resolve this issue, we modeled the structures of kinesin-1 (Kin1), MT, and the Kin1-MT complex using the elastic network model and calculated the residue-dependent responses to a local perturbation in the constructs. Kin1 binding elicits an asymmetric response that is pronounced in α/β-tubulin dimers in the plus end of the MT. Kin1 opens the clefts of multiple plus end α/β-tubulin dimers, creating binding-competent conformations, which is required for processivity. Reciprocally, MT induces correlations between switches I and II in the motor and enhances fluctuations in adenosine 5'-diphosphate and the residues in the binding pocket. Our findings explain both the directionality of stepping and MT effects on a key step in the catalytic cycle of kinesin.