Run length distribution of dimerized kinesin-3 molecular motors: comparison with dimeric kinesin-1

Si-Kao Guo,Peng-Ye Wang,Ping Xie,Xiao-Xuan Shi

doi:10.1038/s41598-019-53550-2

Abstract

Kinesin-3 and kinesin-1 molecular motors are two families of the kinesin superfamily. It has been experimentally revealed that in monomeric state kinesin-3 is inactive in motility and cargo-mediated dimerization results in superprocessive motion, with an average run length being more than 10-fold longer than that of kinesin-1. In contrast to kinesin-1 showing normally single-exponential distribution of run lengths, dimerized kinesin-3 shows puzzlingly Gaussian distribution of run lengths. Here, based on our proposed model, we studied computationally the dynamics of kinesin-3 and compared with that of kinesin-1, explaining quantitatively the available experimental data and revealing the origin of superprocessivity and Gaussian run length distribution of kinesin-3. Moreover, predicted results are provided on ATP-concentration dependence of run length distribution and force dependence of mean run length and dissociation rate of kinesin-3.

Highlights

Kinesin-3 and kinesin-1 molecular motors are two families of the kinesin superfamily
Using Forster resonance energy transfer microscopy in live cells, Soppina et al.[23] showed that while in monomeric state kinesin-3 is inactive in motility, the dimerization results in superprocessive motion, with an average run length of ~ 10 μm, which is more than 10-fold longer than that of kinesin-1
Is the higher MT affinity sufficient to give the superprocessivity of kinesin-3 dimers? While the K-loop enhances the MT affinity, why do mutations of the K-loop have little effect on the superprocessivity of kinesin-3 dimers? More puzzlingly, why do kinesin-3 dimers have approximately a Gaussian form of run length distributions rather than a nearly single-exponential form? The purpose of this work is to address these unclear issues, which is critical to the molecular mechanism of the mechanochemical coupling of kinesin-3 dimers

Summary

Introduction

Kinesin-3 and kinesin-1 molecular motors are two families of the kinesin superfamily. It has been experimentally revealed that in monomeric state kinesin-3 is inactive in motility and cargo-mediated dimerization results in superprocessive motion, with an average run length being more than 10-fold longer than that of kinesin-1. Kinesins are a large superfamily of motor proteins capable of moving on microtubule (MT) filaments by hydrolyzing ATP1–3 They are responsible for a variety of biological functions in cell such as intracellular cargo transport, chromosome segregation, spindle assembly, cytoskeletal organization, etc.[3]. Using Forster resonance energy transfer microscopy in live cells, Soppina et al.[23] showed that while in monomeric state kinesin-3 is inactive in motility, the dimerization results in superprocessive motion, with an average run length of ~ 10 μm, which is more than 10-fold longer than that of kinesin-1. In both states the MT-bound head has the ATPase activity

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