肌球蛋白V的弹性杠杆臂模型
Elastic lever arm model for myosin V
摘要：
我们提出了一个机械化学模型的肌球蛋白V，一个双头进行马达蛋白。我们从一个单独的头部，我们的模型都与4状态循环（分离，与ADP连接。Pi，与ADP连接，没有核苷酸连接），或者与5状态循环（其中的动力冲程是不紧密耦合到磷酸盐释放）的二聚体的属性。在每种状态下，杠杆臂以不同但固定的角度离开头部。杠杆臂本身被描述为弹性杆。两个头部的化学循环仅通过两个杠杆臂之间的机械连接来协调。该模型解释了头部协调显示，铅头只绑定到肌动蛋白后，在拖曳头的权力中风，它只经历了它的权力中风后，拖曳头解开肌动蛋白。这两个模型（4和5状态）再现所观察到的双手运动，并适合测得的力-速度关系。这两个模型之间的主要区别在于运行长度的负载依赖性，这在5状态模型中要弱得多。我们展示了如何在不同条件下系统的持续合成能力测量可以用来区分这两种模型，并确定动力学参数。
英文摘要：
We present a mechanochemical model for myosin V, a two-headed processive motor protein. We derive the properties of a dimer from those of an individual head, which we model both with a 4-state cycle (detached, attached with ADP.Pi, attached with ADP and attached without nucleotide) and alternatively with a 5-state cycle (where the power stroke is not tightly coupled to the phosphate release). In each state the lever arm leaves the head at a different, but fixed, angle. The lever arm itself is described as an elastic rod. The chemical cycles of both heads are coordinated exclusively by the mechanical connection between the two lever arms. The model explains head coordination by showing that the lead head only binds to actin after the power stroke in the trail head and that it only undergoes its power stroke after the trail head unbinds from actin. Both models (4- and 5-state) reproduce the observed hand-over-hand motion and fit the measured force-velocity relations. The main difference between the two models concerns the load dependence of the run length, which is much weaker in the 5-state model. We show how systematic processivity measurement under varying conditions could be used to distinguish between both models and to determine the kinetic parameters.
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