Energy transduction in ATP synthase

Mitochondria, bacteria and chloroplasts use the free energy stored in transmembrane ion gradients to manufacture ATP by the action of ATP synthase. This enzyme consists of two principal domains. The asymmetric membrane-spanning F-0 portion contains the proton channel, and the soluble F-1 portion contains three catalytic sites which cooperate in the synthetic reactions(1). The Bow of protons through F-0 is thought to generate a torque which is transmitted to F-1 by an asymmetric shaft, the coiled-coil gamma-subunit. This acts as a rotating 'cam' within F-1, sequentially releasing ATPs from the three active sites(1-5). The free-energy difference across the inner membrane of mitochondria and bacteria is sufficient to produce three ATPs per twelve protons passing through the motor. It has been suggested that this protonmotive force biases the rotor's diffusion so that F-0 constitutes a rotary motor turning the gamma shaft(6). Here we show that biased diffusion, augmented by electrostatic forces, does indeed generate sufficient torque to account for ATP production. Moreover, the motor's reversibility-supplying torque from ATP hydrolysis in F-1 converts the motor into an efficient proton pump(7)-can also be explained by our model.