Department of Pharmacology, University of Nevada, Reno School of Medicine, Reno, Nevada.
Biophys J. 2022 Apr 5;121(7):1184-1193. doi: 10.1016/j.bpj.2022.02.034. Epub 2022 Feb 19.
Molecular motors play a central role in many biological processes, ranging from pumping blood and breathing to growth and wound healing. Through motor-catalyzed chemical reactions, these nanomachines convert the chemical free energy from ATP hydrolysis into two different forms of mechanical work. Motor enzymes perform reversible work, w, through an intermediate step in their catalyzed reaction cycle referred to as a working step, and they perform Fx work when they move a distance, x, against a force, F. In a powerstroke model, w is performed when the working step stretches a spring within a given motor enzyme. In a chemical-Fx model, w is performed in generating a conserved Fx potential defined external to the motor enzyme. It is difficult to find any common ground between these models even though both have been shown to account for mechanochemical measurements of motor enzymes with reasonable accuracy. Here, I show that, by changing one simple assumption in each model, the powerstroke and chemical-Fx model can be reconciled through a chemical thermodynamic model. The formal and experimental justifications for changing these assumptions are presented. The result is a unifying model for mechanochemical coupling in motor enzymes first presented by A.V. Hill in 1938 that is consistent with single-molecule structural and mechanical data.
分子马达在许多生物过程中起着核心作用，从血液循环和呼吸到生长和伤口愈合。这些纳米机器通过马达催化的化学反应，将 ATP 水解产生的化学自由能转化为两种不同形式的机械功。马达酶通过其催化反应循环中的中间步骤，即工作步骤，进行可逆功 w 的操作，并且当它们在力 F 的作用下移动距离 x 时，它们会进行 Fx 功的操作。在动力冲程模型中，当工作步骤拉伸给定的马达酶内的弹簧时，w 就会被执行。在化学-Fx 模型中，w 是在产生定义为马达酶外部的保守 Fx 势能时执行的。尽管这两种模型都被证明可以合理准确地解释马达酶的机械化学测量，但它们之间很难找到任何共同点。在这里，我表明，通过改变每个模型中的一个简单假设，可以通过化学热力学模型来调和动力冲程和化学-Fx 模型。提出了改变这些假设的形式和实验依据。结果是 1938 年 A.V. Hill 首次提出的用于解释马达酶机械化学耦联的统一模型，该模型与单分子结构和力学数据一致。
