Molecular motors have evolved to transduce chemical energy from ATP into mechanical work to drive essential cellular processes, from muscle contraction to vesicular transport. Dysfunction of these motors is a root cause of many pathologies necessitating the need for intrinsic control over molecular motor function. Herein, we demonstrate that positional isomerism can be used as a simple and powerful tool to control the molecular motor of muscle, myosin. Using three isomers of a synthetic non-nucleoside triphosphate, we demonstrate that myosin's force- and motion-generating capacity can be dramatically altered at both the ensemble and single-molecule levels. By correlating our experimental results with computation, we show that each isomer exerts intrinsic control by affecting distinct steps in myosin's mechanochemical cycle. Our studies demonstrate that subtle variations in the structure of an abiotic energy source can be used to control the force and motility of myosin without altering myosin's structure.

中文翻译：

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非核苷底物的位置异构体对肌球蛋白功能的影响不同

分子马达已经进化为将化学能从 ATP 转换为机械功，以驱动基本的细胞过程，从肌肉收缩到囊泡运输。这些电机的功能障碍是许多病理学的根本原因，需要对分子运动功能进行内在控制。在这里，我们证明了位置异构可以作为一种简单而强大的工具来控制肌肉的分子运动，肌球蛋白。使用合成的非核苷三磷酸的三种异构体，我们证明肌球蛋白的力和运动产生能力可以在整体和单分子水平上发生显着改变。通过将我们的实验结果与计算相关联，我们表明每个异构体通过影响肌球蛋白机械化学循环中的不同步骤来发挥内在控制。