Shanghai Key Laboratory for Contemporary Applied Mathematics, School of Mathematical Sciences, Fudan University, Shanghai, China.
Shanghai Key Laboratory for Contemporary Applied Mathematics, School of Mathematical Sciences, Fudan University, Shanghai, China.
J Biol Chem. 2022 Jun;298(6):101948. doi: 10.1016/j.jbc.2022.101948. Epub 2022 Apr 18.
Kinesin-1 is an ATP-driven, two-headed motor protein that transports intracellular cargoes (loads) along microtubules. The movement of kinesin-1 has generally been modeled according to its correlation with ATP cleavage (forward movement), synthesis (backward movement), or unproductive cleavage (futile consumption). Based on recent experimental observations, we formulate a mechanochemical model for this movement in which the forward/backward/futile cycle can be realized through multiple biochemical pathways. Our results show that the backward motion of kinesin-1 occurs mainly through backward sliding along the microtubule and is usually also coupled with ATP hydrolysis. We also found that with a low external load, about 80% of ATP is wasted (futile consumption) by kinesin-1. Furthermore, at high ATP concentrations or under high external loads, both heads of kinesin-1 are always in the ATP- or ADP ⋅ Pi-binding state and tightly bound to the microtubule, while at low ATP concentrations and low loads, kinesin-1 is mainly in the one-head-bound state. Unless the external load is near the stall force, the motion of kinesin-1 is almost deterministic.
驱动蛋白-1 是一种 ATP 驱动的、双头的马达蛋白，可沿微管运输细胞内货物（负荷）。驱动蛋白-1 的运动通常根据其与 ATP 裂解（前进运动）、合成（后退运动）或无效裂解（无效消耗）的相关性来建模。基于最近的实验观察，我们为这种运动制定了一个机械化学模型，其中可以通过多种生化途径实现前进/后退/无效循环。我们的结果表明，驱动蛋白-1 的后退运动主要通过沿微管向后滑动发生，通常也与 ATP 水解偶联。我们还发现，在低外部负载下，驱动蛋白-1 大约 80%的 ATP 被浪费（无效消耗）。此外，在高 ATP 浓度或高外部负载下，驱动蛋白-1 的两个头部始终处于 ATP 或 ADP ⋅ Pi 结合状态并紧密结合到微管上，而在低 ATP 浓度和低负载下，驱动蛋白-1 主要处于单头部结合状态。除非外部负载接近失速力，否则驱动蛋白-1 的运动几乎是确定的。
