ATP synthase — a marvellous rotary engine of the cell

Key Points ATP synthase is a ubiquitous, highly conserved enzyme that catalyses the formation of ATP from ADP and P i using a unique rotary motor mechanism. The enzyme is located in the inner membrane of mitochondria, in the thylakoid membrane of chloroplasts, and in the plasma membrane of bacteria. Recent analysis of the crystal structure of the enzyme has shown in atomic detail the intricate mechanisms of rotary catalysis. ATP synthase is a large (500 kDa) multisubunit protein, consisting of an intrinsic membrane domain, F o , linked through central and side stalks to a globular catalytic domain, F 1 . The F 1 portion consists of three α- and three β-subunits and a single γδɛ-subunit, whereas F o comprises one a -subunit, two b -subunits and 10–12 c -subunits. The synthesis of ATP is brought about by the rotary motion of the F o F 1 complex: when a large electrochemical potential (proton gradient) flows through the F o subunit, this causes rotation of the F o subunit and, subsequently, F 1 , leading to ATP synthesis. ATP hydrolysis by ATPase — the reverse reaction — induces rotation of the F o rotor in the opposite direction. So, ATP synthase can be viewed as a complex of two motors: an ATP-driven F 1 motor and the proton-driven F o motor. ATP synthase can be thought of as a complex of two motors — the ATP-driven F 1 motor and the proton-driven F o motor — that rotate in opposite directions. The mechanisms by which rotation and catalysis are coupled in the working enzyme are now being unravelled on a molecular scale.