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肌球蛋白-13 MCAK 微管解聚酶的建模研究。

Modeling study of kinesin-13 MCAK microtubule depolymerase.

机构信息

Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China.

出版信息

Eur Biophys J. 2024 Aug;53(5-6):339-354. doi: 10.1007/s00249-024-01718-8. Epub 2024 Aug 2.

DOI:10.1007/s00249-024-01718-8
PMID:39093405
Abstract

Mitotic centromere-associated kinesin (MCAK) motor protein is a typical member of the kinesin-13 family, which can depolymerize microtubules from both plus and minus ends. A critical issue for the MCAK motor is how it performs the depolymerase activity. To address the issue, the pathway of the MCAK motor moving on microtubules and depolymerizing the microtubules is presented here. On the basis of the pathway, the dynamics of both the wild-type and mutant MCAK motors is studied theoretically, which include the full-length MCAK, the full-length MCAK with mutations in the α4-helix of the motor domain, the mutant full-length MCAK with a neutralized neck, the monomeric MCAK and the mutant monomeric MCAK with a neutralized neck. The studies show that a single dimeric MCAK motor can depolymerize microtubules in a processive manner, with either one tubulin or two tubulins being removed per times. The theoretical results are in agreement with the available experimental data. Moreover, predicted results are provided.

摘要

有丝分裂着丝粒相关驱动蛋白(MCAK)是驱动蛋白-13 家族的典型成员,它可以从微管的正端和负端解聚微管。MCAK 马达的一个关键问题是它如何执行解聚酶活性。为了解决这个问题,本文提出了 MCAK 马达在微管上移动并解聚微管的途径。在此基础上,从理论上研究了野生型和突变型 MCAK 马达的动力学,包括全长 MCAK、马达结构域 α4 螺旋突变的全长 MCAK、去中和颈部的突变全长 MCAK、单体 MCAK 和去中和颈部的突变单体 MCAK。研究表明,单个二聚体 MCAK 马达可以以连续的方式解聚微管,每次去除一个或两个微管。理论结果与现有的实验数据一致。此外,还提供了预测结果。

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1
Modeling study of kinesin-13 MCAK microtubule depolymerase.肌球蛋白-13 MCAK 微管解聚酶的建模研究。
Eur Biophys J. 2024 Aug;53(5-6):339-354. doi: 10.1007/s00249-024-01718-8. Epub 2024 Aug 2.
2
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The depolymerase activity of MCAK shows a graded response to Aurora B kinase phosphorylation through allosteric regulation.MCAK 的解聚酶活性通过别构调节对 Aurora B 激酶磷酸化呈现出逐渐增强的反应。
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The C-terminal region of the motor protein MCAK controls its structure and activity through a conformational switch.驱动蛋白MCAK的C末端区域通过构象转换来控制其结构和活性。
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Full-length dimeric MCAK is a more efficient microtubule depolymerase than minimal domain monomeric MCAK.全长二聚体MCAK比最小结构域单体MCAK是一种更有效的微管解聚酶。
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The family-specific α4-helix of the kinesin-13, MCAK, is critical to microtubule end recognition.驱动蛋白-13(MCAK)的家族特异性α4螺旋对于微管末端识别至关重要。
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PLK1 phosphorylates mitotic centromere-associated kinesin and promotes its depolymerase activity.PLK1 磷酸化有丝分裂着丝粒相关驱动蛋白并促进其解聚酶活性。
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A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin.一种人工合成的祖先型驱动蛋白-13 比任何天然的解聚驱动蛋白都能更快地解聚微管。
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本文引用的文献

1
A model of microtubule depolymerization by kinesin-8 motor proteins.微管解聚的动力蛋白 - 8 模型。
Adv Protein Chem Struct Biol. 2024;141:87-122. doi: 10.1016/bs.apcsb.2023.12.002. Epub 2023 Dec 28.
2
Molecular mechanism of interaction between kinesin motors affecting their residence times on microtubule lattice and end.驱动蛋白马达相互作用的分子机制影响其在微管晶格和末端的停留时间。
J Theor Biol. 2023 Aug 21;571:111556. doi: 10.1016/j.jtbi.2023.111556. Epub 2023 Jun 9.
3
Causes, costs and consequences of kinesin motors communicating through the microtubule lattice.
肌球蛋白马达通过微管晶格进行通讯的原因、成本和后果。
J Cell Sci. 2023 Mar 1;136(5). doi: 10.1242/jcs.260735. Epub 2023 Mar 3.
4
Determinant factors for residence time of kinesin motors at microtubule ends.驱动蛋白马达在微管末端停留时间的决定因素。
J Biol Phys. 2023 Mar;49(1):77-93. doi: 10.1007/s10867-022-09623-x. Epub 2023 Jan 16.
5
A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin.一种人工合成的祖先型驱动蛋白-13 比任何天然的解聚驱动蛋白都能更快地解聚微管。
Open Biol. 2022 Aug;12(8):220133. doi: 10.1098/rsob.220133. Epub 2022 Aug 31.
6
Modeling processive motion of kinesin-13 MCAK and kinesin-14 Cik1-Kar3 molecular motors.建模驱动蛋白-13 MCAK 和驱动蛋白-14 Cik1-Kar3 分子马达的定向运动。
Protein Sci. 2021 Oct;30(10):2092-2105. doi: 10.1002/pro.4165. Epub 2021 Aug 20.
7
Single depolymerizing and transport kinesins stabilize microtubule ends.单一解聚和运输驱动蛋白稳定微管末端。
Cytoskeleton (Hoboken). 2021 May;78(5):177-184. doi: 10.1002/cm.21681. Epub 2021 Aug 6.
8
Studies of Conformational Changes of Tubulin Induced by Interaction with Kinesin Using Atomistic Molecular Dynamics Simulations.使用原子分子动力学模拟研究与驱动蛋白相互作用诱导的微管蛋白构象变化。
Int J Mol Sci. 2021 Jun 23;22(13):6709. doi: 10.3390/ijms22136709.
9
The Kinesin-8 Kip3 Depolymerizes Microtubules with a Collective Force-Dependent Mechanism.驱动蛋白-8 Kip3通过一种集体力依赖机制使微管解聚。
Biophys J. 2020 Apr 21;118(8):1958-1967. doi: 10.1016/j.bpj.2020.02.030. Epub 2020 Mar 14.
10
Experimental and theoretical energetics of walking molecular motors under fluctuating environments.波动环境下行走分子马达的实验与理论能量学
Biophys Rev. 2020 Apr;12(2):503-510. doi: 10.1007/s12551-020-00684-7. Epub 2020 Mar 16.