Biased Brownian Motion of KIF1A and the Role of Tubulin's C-Terminal Tail Studied by Molecular Dynamics Simulation.

Yukinobu Mizuhara,Mitsunori Takano

doi:10.3390/ijms22041547

Yukinobu Mizuhara, Mitsunori Takano

Open Access

https://doi.org/10.3390/ijms22041547

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Abstract

KIF1A is a kinesin family protein that moves over a long distance along the microtubule (MT) to transport synaptic vesicle precursors in neurons. A single KIF1A molecule can move toward the plus-end of MT in the monomeric form, exhibiting the characteristics of biased Brownian motion. However, how the bias is generated in the Brownian motion of KIF1A has not yet been firmly established. To elucidate this, we conducted a set of molecular dynamics simulations and observed the binding of KIF1A to MT. We found that KIF1A exhibits biased Brownian motion along MT as it binds to MT. Furthermore, we show that the bias toward the plus-end is generated by the ratchet-like energy landscape for the KIF1A-MT interaction, in which the electrostatic interaction and the negatively-charged C-terminal tail (CTT) of tubulin play an essential role. The relevance to the post-translational modifications of CTT is also discussed.

Highlights

KIF1A, a kinesin-3 family protein, is a molecular motor that moves on the microtubule (MT) over a long distance toward the plus-end of MT
Single molecule experiments demonstrated that the movement of a monomeric KIF1A along the MT is well characterized by biased Brownian motion [1,8,9], and the bias toward the plus-end of the MT is generated when KIF1A binds to the MT [9]
To study the binding of monomeric KIF1A to the MT by molecular dynamics (MD) simulation, we employed a minimal system constituted by a single monomeric KIF1A and a single MT protofilament containing 20 tubulins (Figure 1a)

Summary

Introduction

KIF1A, a kinesin-3 family protein, is a molecular motor that moves on the microtubule (MT) over a long distance toward the plus-end of MT. Single molecule experiments demonstrated that the movement of a monomeric KIF1A along the MT is well characterized by biased Brownian motion [1,8,9], and the bias toward the plus-end of the MT is generated when KIF1A binds to the MT [9]. The importance of one-dimensional Brownian motion and the electrostatic interaction between the K-loop and the CTT has been indicated in the long-distance movement of the dimeric form of KIF1A as well [10,11]

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Results

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