Modeling Motility of the Kinesin Dimer from Molecular Properties of Individual Monomers

TL;DR

This paper models kinesin dimer motility by linking molecular properties of monomers to load-dependent transport behavior, explaining experimental observations and predicting how detachment pathways influence run length.

Contribution

It introduces a model connecting monomer properties to dimer motility under load, explaining ATP dependence and load effects on run length and velocity.

Findings

Run length depends on detachment pathways.

Load-biased head diffusion explains assisting load effects.

ATP dependence of run length is clarified.

Abstract

Conventional kinesin is a homodimeric motor protein that unidirectionally transports organelles along filamentous microtubule (MT) by hydrolyzing ATP molecules. This study shows that the load modulations of ATP turnover and head diffusion are both essential in determining the performance of the dimer under loads. It is found that the consecutive run length of the dimer critically depends upon a few pathways, leading to the detachment of individual heads from MT. Modifying rates for these detachment pathways changes the run length but not the velocity of the dimer, consistent with mutant experiments. The run length may increase with or without the ATP concentration, depending upon a single rate for pure mechanical detachment. This finding provides an explanation to a previous controversy concerning ATP dependence of the run length, and related quantitative predictions of this study can be tested by a future experiment. This study also finds that the experimental observations for assisting loads can be quantitatively explained by load-biased head diffusion. We thus conclude that the dimer motility under resisting as well as assisting loads is governed by essentially the same mechanisms.