Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China.
Eur Biophys J. 2024 Aug;53(5-6):339-354. doi: 10.1007/s00249-024-01718-8. Epub 2024 Aug 2.
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.
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。