Xie Ping, Dou Shuo-Xing, Wang Peng-Ye
Laboratory of Soft Matter Physics, Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100080, China.
Biosystems. 2006 Apr;84(1):24-38. doi: 10.1016/j.biosystems.2005.09.008. Epub 2005 Dec 27.
A hand-over-hand model is presented for the processive movement of two-headed kinesin based on previous structural and biochemical studies. In the model, the ATPase activities of the two heads are regulated by forces, both from internal elasticity and external load, exerted on their neck linkers. The results from the model show that the two heads may be partially coordinated in their ATPase cycles: in the case of backward load or low forward load, the ATPase cycles of its two heads are well coordinated, whereas in the case of high forward load, they are no longer well coordinated. The model gives results that show good quantitative agreement with both previous biochemical and mechanical experimental results such as the limping of homodimers and the dependences of mean velocity on [ATP] and on loads (both positive and negative). Furthermore, using the model we study the kinetics of a number of mutant kinesin homodimers and heterodimers, showing that the two heads' ATPase activities of some of these molecules are not well coordinated and they move processively with low mechanochemical coupling efficiencies even under no load. The theoretical results of ATPase rate per head, moving velocity, and stall force of the motors show good quantitative agreement with the experimental ones. The puzzling dynamic behaviours of mutant homodimeric and heterodimeric kinesins become understandable.
基于之前的结构和生化研究，提出了一种用于双头驱动蛋白进行性运动的手把手模型。在该模型中，两个头部的ATP酶活性受施加在其颈部连接体上的力调节，这些力既来自内部弹性，也来自外部负载。模型结果表明，两个头部在其ATP酶循环中可能部分协调：在向后负载或低向前负载的情况下，其两个头部的ATP酶循环协调良好，而在高向前负载的情况下，它们不再协调良好。该模型给出的结果与之前的生化和力学实验结果在定量上吻合良好，比如同型二聚体的跛行以及平均速度对[ATP]和负载（正负负载）的依赖性。此外，利用该模型我们研究了许多突变驱动蛋白同型二聚体和异型二聚体的动力学，结果表明其中一些分子的两个头部的ATP酶活性协调不佳，并且即使在无负载情况下它们也以低机械化学偶联效率进行性移动。每个头部的ATP酶速率、移动速度和马达的失速力的理论结果与实验结果在定量上吻合良好。突变同型二聚体和异型二聚体驱动蛋白令人困惑的动态行为变得可以理解。
