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Biophys J. 2019 Jun 18;116(12):2266-2274. doi: 10.1016/j.bpj.2019.05.011. Epub 2019 May 18.

A Brownian Ratchet Model Explains the Biased Sidestepping of Single-Headed Kinesin-3 KIF1A.

Author information

1
Center for Molecular and Cellular Bioengineering, B CUBE, Technische Universität Dresden, Dresden, Germany.
2
Department of Physics and Astronomy, Aarhus University, Aarhus, Denmark.
3
Center for Molecular and Cellular Bioengineering, B CUBE, Technische Universität Dresden, Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
4
Departament de Física de la Matèria Condensada, Facultat de Física, University of Barcelona, Barcelona, Spain; University of Barcelona Institute of Complex Systems, University of Barcelona, Barcelona, Spain.
5
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Max Planck Institute for the Physics of Complex Systems, Dresden, Germany; Center for Systems Biology Dresden, Dresden, Germany. Electronic address: oriola@mpi-cbg.de.

Abstract

The kinesin-3 motor KIF1A is involved in long-ranged axonal transport in neurons. To ensure vesicular delivery, motors need to navigate the microtubule lattice and overcome possible roadblocks along the way. The single-headed form of KIF1A is a highly diffusive motor that has been shown to be a prototype of a Brownian motor by virtue of a weakly bound diffusive state to the microtubule. Recently, groups of single-headed KIF1A motors were found to be able to sidestep along the microtubule lattice, creating left-handed helical membrane tubes when pulling on giant unilamellar vesicles in vitro. A possible hypothesis is that the diffusive state enables the motor to explore the microtubule lattice and switch protofilaments, leading to a left-handed helical motion. Here, we study the longitudinal rotation of microtubules driven by single-headed KIF1A motors using fluorescence-interference contrast microscopy. We find an average rotational pitch of ≃1.5μm, which is remarkably robust to changes in the gliding velocity, ATP concentration, microtubule length, and motor density. Our experimental results are compared to stochastic simulations of Brownian motors moving on a two-dimensional continuum ratchet potential, which quantitatively agree with the fluorescence-interference contrast experiments. We find that single-headed KIF1A sidestepping can be explained as a consequence of the intrinsic handedness and polarity of the microtubule lattice in combination with the diffusive mechanochemical cycle of the motor.

PMID:
31155147
PMCID:
PMC6588830
[Available on 2020-06-18]
DOI:
10.1016/j.bpj.2019.05.011

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