Understanding Mechanochemical Coupling in Kinesins Using First-Passage Time Processes

TL;DR

This paper presents a theoretical model using first-passage time processes to analyze the mechanochemical coupling in kinesins, accounting for forward, backward steps, and detachments, aligning well with experimental data.

Contribution

It extends existing models to include irreversible detachments and demonstrates that dwell times are identical across different events, supporting the view that only forward motion couples to ATP hydrolysis.

Findings

Dwell times for all events are the same.

The model accurately describes experimental data.

Only forward motion is coupled to ATP hydrolysis.

Abstract

Kinesins are processive motor proteins that move along microtubules in a stepwise manner, and their motion is powered by the hydrolysis of ATP. Recent experiments have investigated the coupling between the individual steps of single kinesin molecules and ATP hydrolysis, taking explicitly into account forward steps, backward steps and detachments. A theoretical study of mechanochemical coupling in kinesins, which extends the approach used successfully to describe the dynamics of conventional motor proteins, is presented. The possibility of irreversible detachments of kinesins from the microtubules is also explicitly taken into account. Using the method of first- passage times, experimental data on the mechanochemical coupling in kinesins are fully described using the simplest two-state model. It is shown that the dwell times for the kinesin to move one step forward or backward, or to dissociate irreversibly are the same, although the probabilities of these events are different. It is concluded that the current theoretical view, that only the forward motion of the motor protein molecule is coupled to ATP hydrolysis, is consistent with all available experimental observations for kinesins.