School of Information and Communication Technology, Griffith University, 4222, QLD, Australia.
Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, 11365-11155, Iran.
Mol Inform. 2018 Apr;37(4):e1700092. doi: 10.1002/minf.201700092. Epub 2017 Nov 7.
The ability to predict the cellular dynamics of intracellular transport has enormous potential to impact human health. A key transporter is kinesin-1, an ATP-driven molecular motor that shuttles cellular cargos along microtubules (MTs). The dynamics of kinesins depends critically on their unbinding rate from MT, which varies depending on the force direction applied on the motor, i.e. the force-unbinding rate relation is asymmetric. However, it remains unclear how changing the force direction from resisting (applied against the motion direction) to assisting (applied in the motion direction) alters the kinesin's unbinding and stepping. Here, we propose a theoretical model for the influence of the force direction on the stepping dynamics of a single kinesin. The model shows that the asymmetry of the force-unbinding rate relation is independent of ATP concentration. It also reveals that the synthesis of ATP from backward stepping under assisting forces is less likely than under resisting forces. It then finds that the unbinding of kinesin in the strongly MT-bound kinetic states enhances under assisting forces.
预测细胞内运输的细胞动力学具有巨大的潜力来影响人类健康。一个关键的转运蛋白是驱动蛋白-1，它是一种 ATP 驱动的分子马达，可以沿着微管（MT）运输细胞货物。驱动蛋白的动力学取决于它们从 MT 上的解结合速率，这取决于施加在马达上的力的方向，即力-解结合速率关系是不对称的。然而，目前尚不清楚改变力的方向从抵抗（施加在运动方向上）到辅助（施加在运动方向上）如何改变驱动蛋白的解结合和步移。在这里，我们提出了一个理论模型，用于研究力的方向对单个驱动蛋白步移动力学的影响。该模型表明，力-解结合速率关系的不对称性与 ATP 浓度无关。它还揭示了在辅助力下，从向后步移合成 ATP 的可能性小于在抵抗力下。然后发现，在辅助力下，强烈结合 MT 的动力学状态下的驱动蛋白解结合增强。
