Parkin Dan, Takano Mitsunori
Research Institute for Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-Ku, Tokyo169-8555, Japan.
Department of Pure and Applied Physics, Waseda University, 3-8-1 Okubo, Shinjuku-Ku, Tokyo169-8555, Japan.
J Phys Chem B. 2023 Feb 23;127(7):1552-1562. doi: 10.1021/acs.jpcb.2c07875. Epub 2023 Feb 3.
The electrochemical potential difference of protons across the membrane is used to synthesize ATP through the proton-motive rotatory motion of the membrane-embedded region of ATP synthase called F. In this study, we illuminate the unsolved proton-motive rotary mechanism of F on the basis of atomistic simulation with full description of protein, lipid, and water molecules, and highlight the underlying Coulombic design. We first show that a water channel is spontaneously formed at the interfacial region between the rotor (-ring) and the stator (-subunit). The observed water channel is a full channel penetrating the membrane, but a Coulomb barrier by a strictly conserved arginine of the -subunit dominates at the midpoint of the full channel, preventing proton leakage. Our molecular dynamics simulation further demonstrates that the Coulomb attraction between the arginine and the essential glutamic acid of the -subunit drives the -ring rotation. We finally illustrate that the charge-state changes of the glutamic acids, enabled by the electrochemical potential difference of proton and the thermal motion, can produce unidirectional rotation of the -ring.
质子跨膜的电化学势差通过ATP合酶嵌入膜的F区域的质子动力旋转运动来合成ATP。在本研究中，我们基于对蛋白质、脂质和水分子的完整描述的原子模拟，阐明了F未解决的质子动力旋转机制，并突出了潜在的库仑设计。我们首先表明，在转子（-环）和定子（-亚基）之间的界面区域自发形成了一个水通道。观察到的水通道是一个贯穿膜的完整通道，但在完整通道的中点，由-亚基一个严格保守的精氨酸形成的库仑势垒占主导，防止质子泄漏。我们的分子动力学模拟进一步证明，精氨酸与-亚基必需的谷氨酸之间的库仑吸引力驱动-环旋转。我们最终表明，质子的电化学势差和热运动使谷氨酸的电荷状态发生变化，可产生-环的单向旋转。
