Many bacteria enable locomotion by rotating their flagellum. It has been suggested that this rotation is realized by the rotary motion of the stator unit, MotAB, which is driven by proton transfer across the membrane. Recent cryo-electron microscopy studies have revealed a 5:2 MotAB configuration, in which a MotB dimer is encircled by a ring-shaped MotA pentamer. Although the structure implicates the rotary motion of the MotA wheel around the MotB axle, the molecular mechanisms of rotary motion and how they are coupled with proton transfer across the membrane remain elusive. In this study, we built a structure-based computational model for Campylobacter jejuni MotAB, conducted comprehensive protonation-state-dependent molecular dynamics simulations, and revealed a plausible proton-transfer-coupled rotation pathway. The model assumes rotation-dependent proton transfer, in which proton uptake from the periplasmic side to the conserved aspartic acid in MotB is followed by proton hopping to the MotA proton-carrying site, followed by proton export to the CP. We suggest that, by maintaining two of the proton-carrying sites of MotA in the deprotonated state, the MotA pentamer robustly rotates by ∼36° per proton transfer across the membrane. Our results provide a structure-based mechanistic model of the rotary motion of MotAB in bacterial flagellar motors and provide insights into various ion-driven rotary molecular motors.

中文翻译：

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细菌鞭毛马达中 MotAB 旋转机制的理论见解


许多细菌通过旋转鞭毛来实现运动。有人提出，这种旋转是通过定子单元 MotAB 的旋转运动实现的，该旋转运动由跨膜的质子转移驱动。最近的冷冻电子显微镜研究揭示了 5：2 的 MotAB 构型，其中 MotB 二聚体被环形 MotA 五聚体包围。尽管该结构暗示了 MotA 轮围绕 MotB 轴的旋转运动，但旋转运动的分子机制以及它们如何与跨膜的质子转移耦合仍然难以捉摸。在这项研究中，我们建立了一个基于结构的空肠弯曲杆菌 MotAB 计算模型，进行了全面的质子化状态依赖性分子动力学模拟，并揭示了一条合理的质子转移耦合旋转途径。该模型假设旋转依赖性质子转移，其中质子从周质侧摄取到 MotB 中保守的天冬氨酸，然后质子跃迁到 MotA 质子携带位点，然后质子输出到 CP。我们建议，通过将 MotA 的两个质子携带位点保持在去质子化状态，MotA 五聚体在每次质子转移穿过膜时都会稳健地旋转 ∼36°。我们的结果提供了 MotAB 在细菌鞭毛马达中旋转运动的基于结构的机理模型，并提供了对各种离子驱动旋转分子马达的见解。