Biochemical pathways of forward/backward steps of motor protein kinesin-1

TL;DR

This paper develops a mechanochemical model of kinesin-1, revealing multiple biochemical pathways for its forward, backward, and futile cycles, and providing insights into its energy efficiency and motion dynamics under various conditions.

Contribution

It introduces a comprehensive model of kinesin-1's biochemical pathways, including six possible backward pathways, and analyzes its energy consumption and motion behavior.

Findings

Backward motion mainly via sliding in semi-detach state

Approximately 80% ATP is wasted at low load

Kinesin's motion is nearly deterministic under most conditions

Abstract

Kinesin-1 is an ATP-driven, two-headed motor protein that transports intracellular cargoes along microtubule. Based on recent experimental observations, we formulate a mechanochemical model for it, in which forward/backward/futile cycle of kinesin-1 can be realized through multiple biochemical pathways. Our results show that both forward and futile cycles consist of two biochemical pathways, while backward cycle may be realized through six possible pathways. Backward motion of kinesin-1 is mainly through backward sliding along microtubule when it is in semi-detach state, and usually coupled with ATP hydrolysis. Under low external load, about 80\% of ATP is wasted by kinesin-1, and this proportion of waste is almost independent of ATP concentration. At high ATP concentration or under high external load, both heads of kinesin are always in ATP or ADP$\cdot$Pi binding state and bind to microtubule tightly. But at low ATP concentration and low load, kinesin mainly stays at the one head bound state. In contrast to mean run length, the mean run time of kinesin-1 along microtubule decreases with ATP concentration. Unless external load is near the stall force, the motion of kinesin-1 is almost deterministic, not as predicted by usual Browian ratchet models.