Introduction

Kinesin-1 motor is a molecular walking machine constructed with amino acids. The understanding of how those structural elements play their mechanical roles is the key to the understanding of kinesin-1 mechanism.

Methods

Using molecular dynamics simulations, we investigate the role of a helix structure, α4 (also called switch-II helix), of kinesin-1’s motor domain in its processive movement along microtubule.

Results

Through the analysis of the structure and the interactions between α4 and the surrounding residues in different nucleotide-binding states, we find that, mechanically, this helix functions as a shaft for kinesin-1’s motor-domain rotation and, structurally, it is an amphipathic helix ensuring its shaft functioning. The hydrophobic side of α4 consists strictly of hydrophobic residues, making it behave like a lubricated surface in contact with the core β-sheet of kinesin-1’s motor domain. The opposite hydrophilic side of α4 leans firmly against microtubule with charged residues locating at both ends to facilitate its positioning onto the intra-tubulin groove.

Conclusions

The special structural feature of α4 makes for an effective reduction of the conformational work in kinesin-1’s force generation process.

中文翻译：

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驱动蛋白-1 的 α4 螺旋在进行运动中的轴功能。

介绍

Kinesin-1 电机是一种由氨基酸构成的分子行走机器。了解这些结构元件如何发挥其机械作用是理解 kinesin-1 机制的关键。

方法

通过分子动力学模拟，我们研究了驱动蛋白 1 运动域的螺旋结构 α4（也称为开关 II 螺旋）在其沿微管进行运动中的作用。

结果

通过分析α4的结构以及不同核苷酸结合状态下α4与周围残基之间的相互作用，我们发现，从机械角度来看，该螺旋充当驱动蛋白-1运动结构域旋转的轴，从结构角度来看，它是两亲性的螺旋确保其轴的功能。α4 的疏水侧严格由疏水残基组成，使其表现得像与驱动蛋白-1 运动结构域的核心 β-片层接触的润滑表面。α4 的相反亲水侧牢固地靠在微管上，两端带有带电残基，以利于其定位到微管蛋白内凹槽上。

结论

α4的特殊结构特征可以有效减少kinesin-1力产生过程中的构象功。