Kinetic models for the coordinated stepping of cytoplasmic dynein
Kinetic models for the coordinated stepping of cytoplasmic dynein
复制标题
DOI：
10.1063/1.3050098
复制
发表时间：
2009-01-14
影响因子：
4.4
通讯作者：
Elston, Timothy C.
中科院分区：
文献类型：
--
作者：
Tsygankov, Denis;Serohijos, Adrian W. R.;Elston, Timothy C.
要产生沿聚合物轨迹的过程运动，需要马达蛋白将其ATP水解循环与其结构亚基的构象变化相结合。许多实验和理论工作都致力于确定这种化学机械耦合是如何发生的。然而，大多数前进马达的功能是二聚体。因此，充分了解电机的性能还需要了解两个头部的化学机械循环之间的协调。我们考虑了细胞质动力蛋白的一般双头模型，该模型是根据单体动力蛋白的化学机械状态的实验测量而建立的。我们探索了同时满足二聚体蛋白质两个主要要求的不同可能的协调场景：高处理能力(长运行长度)和高运动速度(快速ATP周转)。为了证明这些要求和协调的必要性之间的相互作用，我们首先开发和分析了一个简单的力学模型，用于在没有ATP的情况下进行力诱导的踏步。接下来，我们使用二聚体动力蛋白的化学机械循环的简化模型来建立动力学规则，该模型必须满足的动力学规则才能与单分子实验中发动机性能的最新数据相一致。最后，我们利用这些研究的结果建立了一个完整的二聚体动力蛋白化学机械循环模型，并对该模型进行了分析，以做出实验上可检验的预测。(C)2009年美国物理研究所。[DOI：10.1063/1.3050098]
To generate processive motion along a polymer track requires that motor proteins couple their ATP hydrolysis cycle with conformational changes in their structural subunits. Numerous experimental and theoretical efforts have been devoted to establishing how this chemomechanical coupling occurs. However, most processive motors function as dimers. Therefore a full understanding of the motor's performance also requires knowledge of the coordination between the chemomechanical cycles of the two heads. We consider a general two-headed model for cytoplasmic dynein that is built from experimental measurements on the chemomechanical states of monomeric dynein. We explore different possible scenarios of coordination that simultaneously satisfy two main requirements of the dimeric protein: high processivity (long run length) and high motor velocity (fast ATP turnover). To demonstrate the interplay between these requirements and the necessity for coordination, we first develop and analyze a simple mechanical model for the force-induced stepping in the absence of ATP. Next we use a simplified model of dimeric dynein's chemomechanical cycle to establish the kinetic rules that must be satisfied for the model to be consistent with recent data for the motor's performance from single molecule experiments. Finally, we use the results of these investigations to develop a full model for dimeric dynein's chemomechanical cycle and analyze this model to make experimentally testable predictions. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3050098]