The molecular mechanism of ATP synthase constrains the evolutionary landscape of chemiosmosis.

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.