Macdonald J Emyr, Ashby Paul D
School of Physics and Astronomy, Cardiff University, The Parade, Cardiff CF24 3AA, UK.
Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720.
Biophys J. 2025 Jul 1;124(13):2103-2119. doi: 10.1016/j.bpj.2025.05.017. Epub 2025 May 19.
ATP synthase, the enzyme responsible for regenerating adenosine triphosphate (ATP) in the cell, comprises a proton-translocating motor in the cell membrane (labeled F in bacteria, mitochondria, and chloroplasts), coupled by a common stalk to a catalytic motor F that synthesizes or hydrolyzes ATP, depending on the direction of rotation. The detailed mechanisms of F, F and their coupling in ATP synthase have been elucidated through structural studies, single-molecule experiments, and molecular modeling. The outcomes of this body of work are reviewed with a particular focus on the features of the mechanism that enable the high energy efficiency and reversibility of ATP synthase. Models for the origin of chemiosmosis involve either ATP synthesis (driven by the proton gradient across the membrane) or ATP hydrolysis (for pumping protons out of the cell) as a primary function, the other function being a later development enabled by the coupled nature of the two motors. The mechanism of ATP synthase and the stringent requirements on efficiency to maintain life constrain existing models and the search for the origin of chemiosmosis.
ATP合酶是负责在细胞中再生三磷酸腺苷（ATP）的酶，它在细胞膜中包含一个质子转运马达（在细菌、线粒体和叶绿体中标记为F），通过一个共同的柄与催化马达F相连，F根据旋转方向合成或水解ATP。通过结构研究、单分子实验和分子建模，已经阐明了F、F及其在ATP合酶中的偶联的详细机制。本文特别关注使ATP合酶具有高能效和可逆性的机制特征，对这一系列工作的成果进行了综述。化学渗透起源的模型涉及ATP合成（由跨膜质子梯度驱动）或ATP水解（用于将质子泵出细胞）作为主要功能，另一个功能是由两个马达的偶联性质促成的后期发展。ATP合酶的机制以及对维持生命的效率的严格要求限制了现有模型和对化学渗透起源的探索。
