The intrinsic load-resisting capacity of kinesin

TL;DR

This study models kinesin's molecular mechanics to explain its ability to resist loads and perform backsteps, revealing a ratchet-and-pawl mechanism that accounts for its load-dependent behavior and predicting new features for experimental verification.

Contribution

It introduces a detailed molecular mechanical model of kinesin's load-resisting capacity, highlighting a synergic ratchet-and-pawl mechanism as the basis for its load response.

Findings

Kinesin's load resistance is governed by a ratchet-and-pawl mechanism.

The model explains experimental observations of backwalking under superstall loads.

Predicted features of load-affected motility are verifiable in future experiments.

Abstract

Conventional kinesin is a homodimeric motor protein that is capable of walking unidirectionally along a cytoskeletal filament. While previous experiments indicated unyielding unidirectionality against an opposing load up to the so-called stall force, recent experiments also observed limited processive backwalking under superstall loads. This theoretical study seeks to elucidate the molecular mechanical basis for kinesin's steps over the full range of external loads that can possibly be applied to the dimer. We found that kinesin's load-resisting capacity is largely determined by a synergic ratchet-and-pawl mechanism inherent in the dimer. Load susceptibility of this inner molecular mechanical mechanism underlies kinesin's response to various levels of external loads. Computational implementation of the mechanism enabled us to rationalize major trends observed experimentally in kinesin's stalemate and consecutive back steps. The study also predicts several distinct features of kinesin's load-affected motility, which are seemingly counterintuitive but readily verifiable by future experiment.