Kubo Shintaroh, Okada Yasushi
Department of Cell Biology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Cell Biology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Physics, Graduate School of Science, The University of Tokyo, Tokyo, Japan; Universal Biology Institute and International Research Center for Neurointelligence, The University of Tokyo, Tokyo, Japan; Laboratory for Cell Polarity Regulation, Center for Biosystems Dynamics Research (BDR), RIKEN, Osaka, Japan.
Biophys J. 2025 Mar 18;124(6):891-900. doi: 10.1016/j.bpj.2024.03.013. Epub 2024 Mar 8.
ATP synthase, a crucial enzyme for cellular bioenergetics, operates via the coordinated coupling of an F motor, which presents variable symmetry, and a tripartite F motor. Despite extensive research, the understanding of their coupling dynamics, especially with non-10-fold symmetrical F motors, remains incomplete. This study investigates the coupling patterns between eightfold and ninefold F motors and the constant threefold F motor using coarse-grained molecular dynamics simulations. We unveil that in the case of a ninefold F motor, a 3-3-3 motion is most likely to occur, whereas a 3-3-2 motion predominates with an eightfold F motor. Furthermore, our findings propose a revised model for the coupling method, elucidating that the pathways' energy usage is primarily influenced by F rotation and conformational changes hindered by the b-subunits. Our results present a crucial step toward comprehending the energy landscape and mechanisms governing ATP synthase operation.
ATP合酶是细胞生物能量学中的一种关键酶，它通过具有可变对称性的F₀马达和三方F₁马达的协同偶联来运作。尽管进行了广泛的研究，但对它们的偶联动力学的理解，尤其是对于非10重对称的F₀马达，仍然不完整。本研究使用粗粒度分子动力学模拟研究了八重和九重F₀马达与恒定的三重F₁马达之间的偶联模式。我们发现，在九重F₀马达的情况下，最有可能发生3-3-3运动，而在八重F₀马达中，3-3-2运动占主导。此外，我们的研究结果提出了一种偶联方法的修订模型，阐明了途径的能量使用主要受F旋转和b亚基阻碍的构象变化影响。我们的结果是朝着理解ATP合酶运作的能量格局和机制迈出的关键一步。
