Processivity and Velocity for Motors Stepping on Periodic Tracks
Processivity and Velocity for Motors Stepping on Periodic Tracks
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电机在周期性轨道上行走的过程性和速度
DOI：
10.1101/684696
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
D. Thirumalai
中科院分区：
文献类型：
--
作者：
M. Mugnai;M. Caporizzo;Y. Goldman;D. Thirumalai
加工分子马达通过组装成能够沿着细胞骨架丝进行多个连续步骤的二聚体来实现货物运输。在广为接受的手拉手步进机构中，尾随电机与轨道分离，并将灯丝再次绑在引导位置。这需要 ATP 水解形式的燃料消耗，以及前头和尾随头之间催化循环的协调。然而，存在替代的迈步机制，包括类似尺蠖的运动、后退步和跺脚。所有这些途径是否都与 ATP 水解相关仍有待确定。在这里，为了建立控制渐进运动动力学的原理，我们提出了一个理论框架，其中包括所有替代的步进机制。我们的理论弥合了描述每个头部生化和结构转变的元素速率与实验可测量的量（例如速度、持续性和后退概率）之间的差距。我们的结果是在轨道是周期性和无限的假设下获得的，提供的表达式无论连接中间状态的网络的拓扑如何都成立，因此能够描述任何分子马达的功能。我们将该理论应用到肌球蛋白 VI 上，肌球蛋白 VI 是一种频繁后退的马达，并通过手拉手和尺蠖式的组合向前移动。我们的模型定量地再现了两组实验测量的肌球蛋白 VI 运动的各种可观察结果。该理论用于预测门控机制、后退路径以及作为 ATP 浓度函数的能量消耗。意义陈述 分子马达利用 ATP 水解释放的能量沿着细胞骨架丝运输货物。电机中两个相同的磁头通过相互通信交替行走在极轨上。我们的目标是阐明催化循环中两个头之间的协调是如何产生的。为此，我们创建了一个理论框架，使我们能够将运动的可测量特征（例如运动速度）与前头部和尾部头部的生化速率联系起来，从而将生化活动和运动联系起来。我们通过分析肌球蛋白 VI 的实验数据来说明该理论的有效性，肌球蛋白 VI 频繁地向后移动，并以手拉手和尺蠖状的步骤向前移动。
Processive molecular motors enable cargo transportation by assembling into dimers capable of taking several consecutive steps along a cytoskeletal filament. In the well-accepted hand-over-hand stepping mechanism the trailing motor detaches from the track and binds the filament again in leading position. This requires fuel consumption in the form of ATP hydrolysis, and coordination of the catalytic cycles between the leading and the trailing heads. However, alternative stepping mechanisms exist, including inchworm-like movements, backward steps, and foot stomps. Whether all of these pathways are coupled to ATP hydrolysis remains to be determined. Here, in order to establish the principles governing the dynamics of processive movement, we present a theoretical framework which includes all of the alternative stepping mechanisms. Our theory bridges the gap between the elemental rates describing the biochemical and structural transitions in each head, and the experimentally measurable quantities, such as velocity, processivity, and probability of backward stepping. Our results, obtained under the assumption that the track is periodic and infinite, provide expressions which hold regardless of the topology of the network connecting the intermediate states, and are therefore capable of describing the function of any molecular motor. We apply the theory to myosin VI, a motor that takes frequent backward steps, and moves forward with a combination of hand-over-hand and inchworm-like steps. Our model reproduces quantitatively various observables of myosin VI motility measured experimentally from two groups. The theory is used to predict the gating mechanism, the pathway for backward stepping, and the energy consumption as a function of ATP concentration. Significance Statement Molecular motors harness the energy released by ATP hydrolysis to transport cargo along cytoskeletal filaments. The two identical heads in the motor step alternatively on the polar track by communicating with each other. Our goal is to elucidate how the coordination between the two heads emerges from the catalytic cycles. To do so, we created a theoretical framework that allows us to relate the measurable features of motility, such as motor velocity, with the biochemical rates in the leading and trailing heads, thereby connecting biochemical activity and motility. We illustrate the efficacy of the theory by analyzing experimental data for myosin VI, which takes frequent backward steps, and moves forward by a hand-over-hand and inchworm-like steps.
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DOI：
10.1073/pnas.96.24.13726
发表时间：
1999-11-23
影响因子：
11.1
作者：
De La Cruz, EM;Wells, AL;Sweeney, HL
通讯作者：
Sweeney, HL
肌球蛋白 V 的严格性到后严格性转变：动力学与支持架构之间的联系。
DOI：
10.1016/j.str.2010.01.019
发表时间：
2010
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Tehver,Riina;Thirumalai,D
通讯作者：
Thirumalai,D
大分子动力学的统计动力学。
DOI：
10.1529/biophysj.105.064295
发表时间：
2005
期刊：
Biophysical journal.
影响因子：
--
作者：
Shaevitz,JoshuaW;Block,StevenM;Schnitzer,MarkJ
通讯作者：
Schnitzer,MarkJ
进行性肌球蛋白的杠杆臂力学。
影响因子：
3.4
作者：
Sun,Yujie;Goldman,YaleE
通讯作者：
Goldman,YaleE
影响因子：
16
作者：
Sun, Yujie;Schroeder, Harry W., III;Goldman, Yale E.
通讯作者：
Goldman, Yale E.