Design principles governing the motility of myosin V
Design principles governing the motility of myosin V
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DOI：
10.1073/pnas.1312393110
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发表时间：
2013-10-22
影响因子：
11.1
通讯作者：
Thirumalai, D.
中科院分区：
文献类型：
--
作者：
Hinczewski, Michael;Tehver, Riina;Thirumalai, D.
分子运动肌球蛋白V（MyoV）在步进过程中表现出广泛的途径，这与其生物学功能密切相关。其中最好的理解是通过摆动杠杆臂向肌动蛋白丝的正端移动而进行的双手交替步进。单分子实验也表明，马达“跺脚”，一只手分离和重新绑定到同一地点，并在足够的负荷下后退。MyoV的负载依赖性步进途径的完整分类，以及这些受电机结构和机械化学约束的程度尚不清楚。使用聚合物模型，我们开发了一个分析理论来描述最小的物理特性，支配电机动力学。我们解决了头到达目标结合位点的第一次通过问题，调查向后的负载，应变的竞争效应在领先的头部偏置扩散的方向的目标，和优先结合的可能性，向前的网站由于恢复中风。该理论再现了各种实验数据，包括动力冲程和缓慢扩散的搜索制度的平均轨迹的分离头，和力的依赖性的向前向后的步长比，运行长度，和速度。我们推导出一个失速力公式，由杠杆臂的顺应性和化学循环速率。通过探索MyoV设计空间，我们预测它是一个强大的电机，其动力学行为不会受到合理的扰动反应周期和杠杆臂结构变化的影响。
The molecular motor myosin V (MyoV) exhibits a wide repertoire of pathways during the stepping process, which is intimately connected to its biological function. The best understood of these is the hand-over-hand stepping by a swinging lever arm movement toward the plus end of actin filaments. Single-molecule experiments have also shown that the motor "foot stomps," with one hand detaching and rebinding to the same site, and back-steps under sufficient load. The complete taxonomy of MyoV's load-dependent stepping pathways, and the extent to which these are constrained by motor structure and mechanochemistry, are not understood. Using a polymer model, we develop an analytical theory to describe the minimal physical properties that govern motor dynamics. We solve the first-passage problem of the head reaching the target-binding site, investigating the competing effects of backward load, strain in the leading head biasing the diffusion in the direction of the target, and the possibility of preferential binding to the forward site due to the recovery stroke. The theory reproduces a variety of experimental data, including the power stroke and slow diffusive search regimes in the mean trajectory of the detached head, and the force dependence of the forward-to-backward step ratio, run length, and velocity. We derive a stall force formula, determined by lever arm compliance and chemical cycle rates. By exploring the MyoV design space, we predict that it is a robust motor whose dynamical behavior is not compromised by reasonable perturbations to the reaction cycle and changes in the architecture of the lever arm.