How subunit coupling produces the -subunit rotary motion in F1-ATPase

FoF1-ATP synthase manufactures the energy ‘‘currency,’’ ATP, of living cells. The soluble F1 portion, called F1-ATPase, can act as a rotary motor, with ATP binding, hydrolysis, and product release, inducing a torque on the -subunit. A coarse-grained plastic network model is used to show at a residue level of detail how the conformational changes of the catalytic -subunits act on the -subunit through repulsive van der Waals interactions to generate a torque that drives unidirectional rotation, as observed experimentally. The simulations suggest that the calculated 85° substep rotation is driven primarily by ATP binding and that the subsequent 35° substep rotation is produced by product release from one -subunit and a concomitant binding pocket expansion of another -subunit. The results of the simulation agree with single-molecule experiments [see, for example, Adachi K, et al. (2007) Cell 130:309– 321] and support a tri-site rotary mechanism for F1-ATPase under physiological condition.