The torsional mechanism of energy transfer in ATP synthase

ATP synthase (or F1F0 ATPase) is the central enzyme in biological energy conversion, synthesizing ATP from ADP and inorganic phosphate using the free energy derived from protonmotive force. This large enzyme complex (with an overall molecular weight of 520,000 in Escherichia coli) consists of two major parts: a water-soluble F-1 containing three alpha, three beta and one copy each of the gamma, delta and epsilon subunits and a membrane-embedded F-0 composed of one a, two b and twelve c subunits, The mechanism of coupling proton translocation through F-0 to gamma-epsilon subunit rotation in F-1 is unknown. Here we propose and formulate the novel concept of a torsional mechanism for energy transfer and ATP synthesis in ATP synthase. We show how the protonmotive torque is transmitted from F-0 to F-1 and elucidate how energy is stored and transferred in this remarkable enzyme. The recent observation that an enzyme form where all three catalytic sites are occupied by bound nucleotide occurs during ATP synthesis provides strong experimental support for our proposed mechanism. A motion picture of the cycle of events at the catalytic sites of ATP synthase is also presented for the first time.