How subunit coupling produces the γ-subunit rotary motion in F 1 -ATPase

Abstract

F(o)F(1)-ATP synthase manufactures the energy "currency," ATP, of living cells. The soluble F(1) portion, called F(1)-ATPase, can act as a rotary motor, with ATP binding, hydrolysis, and product release, inducing a torque on the gamma-subunit. A coarse-grained plastic network model is used to show at a residue level of detail how the conformational changes of the catalytic beta-subunits act on the gamma-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 degrees substep rotation is driven primarily by ATP binding and that the subsequent 35 degrees substep rotation is produced by product release from one beta-subunit and a concomitant binding pocket expansion of another beta-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 F(1)-ATPase under physiological condition.