How kinesin waits for ATP affects the nucleotide and load dependence of the stepping kinetics

TL;DR

This paper develops a theoretical model to clarify the waiting state of kinesin during stepping, predicting measurable differences in behavior that can resolve existing experimental controversies about ATP binding mechanisms.

Contribution

The authors introduce a new theory that accurately predicts kinesin's stepping kinetics and proposes a specific experimental measurement to distinguish between competing hypotheses.

Findings

Predicted the randomness parameter varies with ATP concentration and load.

Identified a measurable difference to resolve the kinesin waiting state controversy.

Provided a framework to interpret experimental data on kinesin stepping.

Abstract

Dimeric molecular motors walk on polar tracks by binding and hydrolyzing one ATP per step. Despite tremendous progress, the waiting state for ATP binding in the well-studied kinesin that walks on microtubule (MT), remains controversial. One experiment suggests that in the waiting state both heads are bound to the MT, while the other shows that ATP binds to the leading head after the partner head detaches. To discriminate between these two scenarios, we developed a theory to calculate accurately several experimentally measurable quantities as a function of ATP concentration and resistive force. In particular, we predict that measurement of the randomness parameter could discriminate between the two scenarios for the waiting state of kinesin, thereby resolving this standing controversy.