Operation mechanism of F_oF₁‐adenosine triphosphate synthase revealed by its structure and dynamics

Abstract

F o F 1 -Adenosine triphosphate (ATP) synthase, a complex of two rotary motor proteins, reversibly converts the electrochemical potential of protons across the cell membrane into phosphate transfer potential of ATP to provide the energy currency of the cell. The water-soluble motor is F 1 -ATPase, which possesses ATP synthesis/hydrolysis catalytic sites. Isolated F 1 hydrolyses ATP to rotate the rotary shaft against the stator ring. The membrane-embedded motor is F o , which is driven by proton flow down the proton electrochemical potential. In the F o F 1 complex, the direction of mechanical rotation, the chemical reaction, and the proton transport are determined by the relative amplitudes between the Gibbs free energy of the ATP hydrolysis reaction and the electrochemical potential of protons across the membrane. Therefore, F o F 1 -ATP synthase is a highly efficient molecular device in which the chemical, mechanical, and potential energies are tightly and reversibly converted. In this critical review, we summarize our latest knowledge about the operation mechanism of this sophisticated nanomachine, revealed by its structure and dynamics.

Cryo-EM structures of the autoinhibited E. coli ATP synthase in three rotational states

“…This molecular generator couples ion flow across membranes with the addition of inorganic phosphate (Pi) to ADP thereby generating ATP (Iino and Noji, 2013; Stewart et al, 2014). Most bacteria, including Escherichia coli have only one type of rotary ATPase, referred to as F-type ATPase.…”

Molecular machines – a new dimension of biological sciences

“…Both elements are embedded in the lipid bilayer of the mitochondria inner membrane. The rotation of the rotor is driven by the electrochemical potential difference stored across the inner mitochondrial membrane (the strength of the electric field involved is of the order of 50 x 10 6 V/m) [62,63]. At the stator/rotor interface there are two half-channels, as schematically illustrated in Fig.…”

“…The elucidation of the F 0 F 1 ATPase required application of various experimental techniques, including atomic force microscopy imaging, crystallography, single molecule imaging, electron microscopy, and lab-on-the-chip technology, as well as construction of computational models [62,[66][67][68][69][70]. In the cell any molecular machine functions in a complex system of other devices and molecular structures.…”

“…Since the γ subunit mechanically connects the F 0 and F 1 parts, the rotation of the F 1 rotor, powered by the proton flux, is transmitted to the F 0 cap, where the three ATP binding sites are sequentially altered, producing three ATP molecules per rotation [2,53,57,[61][62][63]65]. The elucidation of the F 0 F 1 ATPase required application of various experimental techniques, including atomic force microscopy imaging, crystallography, single molecule imaging, electron microscopy, and lab-on-the-chip technology, as well as construction of computational models [62,[66][67][68][69][70].…”

Thiol oxidation is crucial in the desensitization of the mitochondrial F1FO-ATPase to oligomycin and other macrolide antibiotics

“…Conversely, through a counterclockwise rotation driven by ATP hydrolysis by F 1 , the same enzyme complex converts the Gibbs free energy of hydrolysis in uphill proton transport through F O , thus re-energizing mitochondria [1][2][3]. The bi-functional capability of the mitochondrial enzyme complex, a unique example of chemo-mechanical coupling in biological systems, is long known to be specifically inhibited by oligomycins (OLIGs) [4].…”