A Model for Chemomechanical Coupling of Kinesin-3 Motor

IF 2.3 4区 医学 Q3 BIOPHYSICS Cellular and molecular bioengineering Pub Date : 2024-02-18 DOI:10.1007/s12195-024-00795-1
Ping Xie
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Abstract

Introduction

Kinesin-3 motor, which is in the monomeric and inactive form in solution, after cargo-induced dimerization can step on microtubules towards the plus end with a high velocity and a supperprocessivity, which is responsible for transporting the cargo in axons and dendrites. The kinesin-3 motor has a large initial landing rate to microtubules and spends the majority of its stepping cycle in a one-head-bound state. Under the load the kinesin-3 motor can dissociate more readily than the kinesin-1 motor.

Methods

To understand the physical origin of the peculiar features for the kinesin-3 motor, a model is presented here for its chemomechanical coupling. Based on the model the dynamics of the motor under no load, under the ramping load and under the constant load is studied analytically.

Results

The theoretical results explain well the available experimental data under no load and under the ramping load. For comparison, the corresponding available experimental data for the kinesin-1 motor under the ramping load are also explained. The predicted results of the velocity, dissociation rate and run length versus the constant load for the kinesin-3 motor are provided.

Conclusions

The study has strong implications for the chemomechanical coupling mechanism of the kinesin-3 dimer. The origin of the kinesin-3 dimer in the predominant one-head-bound state is due to the fact that the rate of ATP transition to ADP in the trailing head is much larger than that of ADP release from the MT-bound head. The study shows that the kinesin-3 ADP-head has an evidently longer interaction distance with microtubule than the kinesin-1 ADP-head, explaining why in the initial ADP state the kinesin-3 motor has the much larger landing rate than the kinesin-1 motor and why under the load the kinesin-3 motor can dissociate more readily than the kinesin-1 motor.

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驱动蛋白-3 马达的化学机械耦合模型
引言 驱动蛋白-3 马达在溶液中是单体和非活性形式,在货物诱导二聚化后可以在微管上以较高的速度和较低的过程活性向加端踏步,从而负责在轴突和树突中运输货物。驱动蛋白-3 马达在微管上的初始着陆率很大,其步进周期的大部分时间都处于单头束缚状态。为了理解驱动蛋白-3 马达特殊特征的物理来源,本文提出了一个驱动蛋白-3 马达的化学机械耦合模型。结果理论结果很好地解释了空载和斜坡载荷下的实验数据。为便于比较,还对斜坡载荷下驱动蛋白-1 马达的相应实验数据进行了解释。结论 本研究对驱动蛋白-3 二聚体的化学机械耦合机理具有重要意义。驱动蛋白-3 的二聚体主要处于单头结合态, 这是因为尾部的 ATP 转化为 ADP 的速率远大于 MT 结合头部的 ADP 释放速率.研究表明,驱动蛋白-3 的 ADP 头与微管的相互作用距离明显长于驱动蛋白-1 的 ADP 头,这就解释了为什么在最初的 ADP 状态下,驱动蛋白-3 的马达比驱动蛋白-1 的马达有更大的着陆速率,以及为什么在负载下驱动蛋白-3 的马达比驱动蛋白-1 的马达更容易解离。
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来源期刊
CiteScore
5.60
自引率
3.60%
发文量
30
审稿时长
>12 weeks
期刊介绍: The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.
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