Key Points
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ATP synthase is a ubiquitous, highly conserved enzyme that catalyses the formation of ATP from ADP and Pi using a unique rotary motor mechanism.
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The enzyme is located in the inner membrane of mitochondria, in the thylakoid membrane of chloroplasts, and in the plasma membrane of bacteria.
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Recent analysis of the crystal structure of the enzyme has shown in atomic detail the intricate mechanisms of rotary catalysis.
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ATP synthase is a large (500 kDa) multisubunit protein, consisting of an intrinsic membrane domain, Fo, linked through central and side stalks to a globular catalytic domain, F1.
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The F1 portion consists of three α- and three β-subunits and a single γδɛ-subunit, whereas Fo comprises one a-subunit, two b-subunits and 10–12 c-subunits.
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The synthesis of ATP is brought about by the rotary motion of the FoF1 complex: when a large electrochemical potential (proton gradient) flows through the Fo subunit, this causes rotation of the Fo subunit and, subsequently, F1, leading to ATP synthesis.
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ATP hydrolysis by ATPase — the reverse reaction — induces rotation of the Fo rotor in the opposite direction. So, ATP synthase can be viewed as a complex of two motors: an ATP-driven F1 motor and the proton-driven Fo motor.
Abstract
ATP synthase can be thought of as a complex of two motors — the ATP-driven F1 motor and the proton-driven Fo motor — that rotate in opposite directions. The mechanisms by which rotation and catalysis are coupled in the working enzyme are now being unravelled on a molecular scale.
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Acknowledgements
We are grateful to A. Leslie and J. Walker for providing us with the preprint of their paper on the structure of (ADP·AlF4−)2F1. We also thank T. Suzuki and K. Tsukuda for their assistance in the preparation of the figures.
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Glossary
- ELECTROCHEMICAL POTENTIAL GRADIENT
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When two aqueous phases are separated by a membrane, the electrochemical potential difference of H+ between the two phases is expressed as Δ\(\overline{μ}\)H+ = FΔΨ−2.3RTΔpH, where F is the Faraday constant, ΔΨ is the electric potential difference between two phases, R is the gas constant, T is the absolute temperature and ΔpH is pH difference between two phases.
- SWITCH II REGION
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The β-subunit of F1 has a region that is topologically equivalent to the switch II region of guanine-nucleotide binding (G) proteins, which changes the conformation in response to the interconversion of GTP and GDP.
- P-LOOP
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Various ATP-metabolizing proteins contain a consensus sequence Gly-X-X-Gly-X-Gly-Lys-Thr (X is variable). This sequence is found in a loop connecting a β-strand (adjacent to a β-strand of switch II region) and an α-helix. The lysine and threonine residues in the P-loop are recruited for binding the phosphate moiety of nucleotides.
- V-ATPASE
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V-ATPase is responsible for ATP synthesis in archaebacteria and a small number of eubacteria. In eukaryotic cells, it works as a proton-translocating machinery driven by ATP hydrolysis, and it is responsible for the acidification of lysosome lumens, chromaffin granules and vacuoles.
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Yoshida, M., Muneyuki, E. & Hisabori, T. ATP synthase — a marvellous rotary engine of the cell. Nat Rev Mol Cell Biol 2, 669–677 (2001). https://doi.org/10.1038/35089509
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DOI: https://doi.org/10.1038/35089509
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