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驱动蛋白的作用机制与调控

Mechanism and regulation of kinesin motors.

作者信息

Yildiz Ahmet

机构信息

Physics Department, University of California at Berkeley, Berkeley, CA, USA.

Department of Molecular and Cellular Biology, University of California at Berkeley, Berkeley, CA, USA.

出版信息

Nat Rev Mol Cell Biol. 2025 Feb;26(2):86-103. doi: 10.1038/s41580-024-00780-6. Epub 2024 Oct 11.

Abstract

Kinesins are a diverse superfamily of microtubule-based motors that perform fundamental roles in intracellular transport, cytoskeletal dynamics and cell division. These motors share a characteristic motor domain that powers unidirectional motility and force generation along microtubules, and they possess unique tail domains that recruit accessory proteins and facilitate oligomerization, regulation and cargo recognition. The location, direction and timing of kinesin-driven processes are tightly regulated by various cofactors, adaptors, microtubule tracks and microtubule-associated proteins. This Review focuses on recent structural and functional studies that reveal how members of the kinesin superfamily use the energy of ATP hydrolysis to transport cargoes, depolymerize microtubules and regulate microtubule dynamics. I also survey how accessory proteins and post-translational modifications regulate the autoinhibition, cargo binding and motility of some of the best-studied kinesins. Despite much progress, the mechanism and regulation of kinesins are still emerging, and unresolved questions can now be tackled using newly developed approaches in biophysics and structural biology.

摘要

驱动蛋白是一个多样化的基于微管的马达超家族,在细胞内运输、细胞骨架动力学和细胞分裂中发挥着重要作用。这些马达共享一个特征性的马达结构域,该结构域为沿微管的单向运动和力的产生提供动力,并且它们拥有独特的尾部结构域,可募集辅助蛋白并促进寡聚化、调节和货物识别。驱动蛋白驱动过程的位置、方向和时间受到各种辅助因子、衔接蛋白、微管轨道和微管相关蛋白的严格调控。本综述重点关注最近的结构和功能研究,这些研究揭示了驱动蛋白超家族的成员如何利用ATP水解的能量来运输货物、解聚微管并调节微管动力学。我还概述了辅助蛋白和翻译后修饰如何调节一些研究得最透彻的驱动蛋白的自身抑制、货物结合和运动性。尽管取得了很大进展,但驱动蛋白的机制和调控仍在不断涌现,现在可以使用生物物理学和结构生物学中新开发的方法来解决未解决的问题。

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