Mitochondria, bacteria and chloroplasts use the free energy stored in
transmembrane ion gradients to manufacture ATP by the action of ATP sy
nthase. This enzyme consists of two principal domains. The asymmetric
membrane-spanning F-0 portion contains the proton channel, and the sol
uble 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,
tile 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 b
acteria 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 t
urning the gamma shaft(6). Here we show that biased diffusion, augment
ed by electrostatic forces, does indeed generate sufficient torque to
account for ATP production. Moreover, the motor's reversibility-supply
ing torque from ATP hydrolysis in F-1 converts the motor into an effic
ient proton pump(7)-can also be explained by our model.