Mechanism of the F1F0-type ATP synthase, a biological rotary motor
Trends in Biochemical SciencesPublished 1 March 2002
Roderick Capaldi, Robert Aggeler
Citations328
SJR quartileQ1
SJR score4.16
SNIP2.34
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TL;DR
Evidence for the function of the rotary motor, from structural, genetic and biophysical studies, is reviewed here, and some uncertainties and remaining mysteries of the enzyme mechanism are also discussed.
Abstract
The F(1)F(0)-type ATP synthase is a key enzyme in cellular energy interconversion. During ATP synthesis, this large protein complex uses a proton gradient and the associated membrane potential to synthesize ATP. It can also reverse and hydrolyze ATP to generate a proton gradient. The structure of this enzyme in different functional forms is now being rapidly elucidated. The emerging consensus is that the enzyme is constructed as two rotary motors, one in the F(1) part that links catalytic site events with movements of an internal rotor, and the other in the F(0) part, linking proton translocation to movements of this F(0) rotor. Although both motors can work separately, they must be connected together to interconvert energy. Evidence for the function of the rotary motor, from structural, genetic and biophysical studies, is reviewed here, and some uncertainties and remaining mysteries of the enzyme mechanism are also discussed.
Keywords
Biochemistry, Genetics and Molecular Biology
NatureStructure at 2.8 Â resolution of F1-ATPase from bovine heart mitochondria
3,011 Citations1994Jan Pieter Abrahams, Andrew G. W. Leslie +2 more
The crystal structure of bovine mitochondrial F1-ATPase determined at 2.8 Å resolution supports a catalytic mechanism in intact ATP synthase in which the three catalytic subunits are in different states of the catalytic cycle at any instant.
NatureDirect observation of the rotation of F1-ATPase
2,244 Citations1997Hiroyuki Noji, Ryohei Yasuda +2 more
It is shown that a single molecule of F1-ATPase acts as a rotary motor, the smallest known, by direct observation of its motion by attaching a fluorescent actin filament to the γ-subunit as a marker, which enabled us to observe this motion directly.
ScienceMolecular Architecture of the Rotary Motor in ATP Synthase
1,261 Citations1999Daniela Stock, Andrew G. W. Leslie +1 more
An electron density map obtained from crystals of a subcomplex of yeast mitochondrial ATP synthase shows a ring of 10 c subunits whose extensive contact between the c ring and the stalk suggests that they may rotate as an ensemble during catalysis.
Biochimica et Biophysica Acta (BBA) - BioenergeticsThe binding change mechanism for ATP synthase — Some probabilities and possibilities
1,019 Citations1993Paul D. Boyer
Conformational changes and catalysis, the uniqueness of the ATP synthase structure and the role of unfolded protein structure in mechanism are discussed.
NatureResolution of distinct rotational substeps by submillisecond kinetic analysis of F1-ATPase
840 Citations2001Ryohei Yasuda, Hiroyuki Noji +3 more
It is shown by high-speed imaging that the 120° step consists of roughly 90° and 30° substeps, each taking only a fraction of a millisecond, which supports the binding-change model for ATP synthesis by reverse rotation of F1-ATPase.
Proceedings of the National Academy of SciencesAngiostatin binds ATP synthase on the surface of human endothelial cells
525 Citations1999Tammy L. Moser, M. Sharon Stack +7 more
Binding of angiostatin to the alpha/beta-subunits of ATP synthase on the cell surface may mediate its antiangiogenic effects and the down-regulation of endothelial cell proliferation and migration.
Trends in Biochemical SciencesATP synthase: an electrochemical ransducer with rotatory mechanics
508 Citations1997Wolfgang Junge, Holger Lill +1 more
How ion flow through the membrane-intrinsic portion, F0, may generate torque and how this might be transmitted between stator and rotor to finally expel spontaneously formed ATP from F1 into water is discussed.
Proceedings of the National Academy of SciencesRotation of subunits during catalysis by Escherichia coli F1-ATPase.
463 Citations1995T. Michael Duncan, Vladimir V. Bulygin +3 more
The results demonstrate that gamma subunit rotates relative to the beta subunits during catalysis, and similar reactivities of unlabeled and radiolabeled beta sub units with gamma C87 upon reoxidation.
CellStructure of Bovine Mitochondrial F1-ATPase with Nucleotide Bound to All Three Catalytic Sites
448 Citations2001R.I. Menz, John E. Walker +1 more
A catalytic scheme for hydrolysis (and synthesis) at physiological rates and a mechanism for the ATP-driven rotation of the gamma subunit are proposed based on the crystal structures of the bovine enzyme.
Nature Structural BiologyThe structure of the central stalk in bovine F(1)-ATPase at 2.4 A resolution.
446 Citations2000Andrew G. W. Leslie, John E. Walker +2 more
The central stalk in ATP synthase is made of γ, δ and ɛ subunits in the mitochondrial enzyme, and with crystals of F1-ATPase inhibited with dicyclohexylcarbodiimide, the complete structure was revealed.
ScienceMechanical Rotation of the c Subunit Oligomer in ATP Synthase (F <sub>0</sub> F <sub>1</sub> ): Direct Observation
445 Citations1999Yoshihiro Sambongi, Yuko Iko +7 more
C coupled rotation may be essential for energy coupling between proton transport through F0 and ATP hydrolysis or synthesis in F1, found in mitochondria or bacterial membranes.
Journal of Biological ChemistryA mechanism of proton translocation by F1F0 ATP synthases suggested by double mutants of the a subunit.
337 Citations1994Steven B. Vik, Barbara J. Antonio
A novel mechanism of proton translocation by F1F0 ATP synthases that includes a rotating oligomer of c subunits, in which the Asp61 of two c subunit simultaneously interact with Glu219 and Arg210 of the a subunit, can be adapted for both mitochondrial and sodium-driven bacterial ATP synthase.
BiochemistrySolution Structure of the Transmembrane H<sup>+</sup>-Transporting Subunit c of the F<sub>1</sub>F<sub>o</sub> ATP Synthase
280 Citations1998Mark E. Girvin, Vinit K. Rastogi +3 more
The shape and charge distribution of the molecular surface of the monomericprotein suggest a packing arrangement for the oligomeric protein in the F0 complex, with the front face of one monomer packing favorably against the back face of a second monomer.
Philosophical Transactions of the Royal Society B Biological SciencesA rotary molecular motor that can work at near 100% efficiency
271 Citations2000Kazuhiko Kinosita, Ryohei Yasuda +2 more
In vitro, it is confirmed in vitro that F1 indeed does ca.
FEBS LettersF‐ATPase: specific observation of the rotating c subunit oligomer of EF<sub>o</sub>EF<sub>1</sub>
190 Citations2000Oliver Pänke, Karin Gumbiowski +2 more
Biochimica et Biophysica Acta (BBA) - BioenergeticsATP synthase: what we know about ATP hydrolysis and what we do not know about ATP synthesis
168 Citations2000Joachim Weber, Alan E. Senior
A speculative model for ATP synthesis is offered and measurement of catalytic site occupancy and ligand binding affinity changes during net ATP synthesis are much needed.
Nature Structural BiologyStructure of the gamma-epsilon complex of ATP synthase.
154 Citations2000Matthew C. J. Wilce, Andrew Rodgers
The crystal structure of a complex of the ɛ-subunit and the central domain of the γ- subunit refined at 2.1 Å resolution reveals how rotation of these subunits causes large conformational changes in F1, and thereby provides new insights into energy coupling between Fo and F1.
Journal of Biological ChemistryCross-linking of the δ Subunit to One of the Three α Subunits Has No Effect on Functioning, as Expected if δ Is a Part of the Stator That Links the F1 and F0 Parts of the Escherichia coli ATP Synthase
143 Citations1997Isla Ogilvie, Robert Aggeler +1 more
It is argued that the delta subunit forms a portion of the stator linking F1 to F0, near the top of the alpha-beta hexagon and not in the stalk region, as fixing the delta to the alpha by cross-linking does not greatly impair either the ATPase function of the enzyme, or coupled proton translocation.
Proceedings of the National Academy of SciencesRotation of the c subunit oligomer in fully functional F <sub>1</sub> F <sub>o</sub> ATP synthase
137 Citations2001Satoshi P. Tsunoda, Robert Aggeler +2 more
It is shown that the ring of c subunits in the F(o) part moves along with the gamma and epsilon subunits, and unequivocally place the c subunit oligomer in the rotor part of this molecular machine.
Journal of Biological ChemistryDisulfide Bond Formation between the COOH-terminal Domain of the β Subunits and the γ and ε Subunits of the Escherichia coli F1-ATPase
133 Citations1995Robert Aggeler, Margaret A. Haughton +1 more
The results show that the parts of around residue 87 (a short α-helix) and the subunit interact with different β subunits that are an essential part of the cooperativity of the enzyme.
FEBS LettersMolecular imaging of <i>Escherichia coli</i> F<sub>0</sub>F<sub>1</sub>‐ATPase in reconstituted membranes using atomic force microscopy
120 Citations1996Kunio Takeyasu, Hiroshi Omote +4 more
The structure of Escherichia coli F0F1‐ATPase (ATP synthase), and its F0 sector reconstituted in lipid membranes was analyzed using atomic force microscopy (AFM) by tapping‐mode operation to suggest inherently asymmetric assemblies of the subunits in the F0sector.
FEBS LettersInter‐subunit rotation and elastic power transmission in F<sub>0</sub>F<sub>1</sub>‐ATPase
118 Citations2001Wolfgang Junge, Oliver Pänke +4 more
It is considered as essential, not only for the robust operation of this ubiquitous enzyme under symmetry mismatch, but also for a high turnover rate under load of the two counteracting and stepping motors/generators.
FEBS LettersTopographical structure of membrane‐bound <i>Escherichia coli</i> F<sub>1</sub>F<sub>0</sub> ATP synthase in aqueous buffer
115 Citations1996Seema Singh, Paola Turina +3 more
The results support models in which the F0 complex contains a ring of 9–12 c subunits with the b subunits located outside this ring, and show that scanning force microscopy is able to provide structural information on membrane proteins of molecular mass less than 200 000 Da.
Biochimica et Biophysica Acta (BBA) - Reviews on BioenergeticsHypothesis the mecanism of ATP synthase conformational change by rotation of the b-subunit
112 Citations1984G B Cox, David A. Jans +3 more
Biochimica et Biophysica Acta (BBA) - BioenergeticsCatalytic site forms and controls in ATP synthase catalysis
107 Citations2000Paul D. Boyer
A suggested minimal scheme for substrate binding by and interconversion of three forms of the catalytic sites of the ATP synthase is presented, and a key step is suggested in which proton translocation begins to deform an open site so as to increase the affinity for ADP and P(i) and yield tightly bound ATP in one binding change.
Proceedings of the National Academy of SciencesLigand-dependent structural variations in Escherichia coli F1 ATPase revealed by cryoelectron microscopy.
101 Citations1990Edward P. Gogol, Ema Johnston +2 more
Domains within the ECF1 structure, either the central mass or a domain including the epsilon subunit, move in the enzyme in response to ligand binding, suggesting that this movement is involved in coupling catalytic sites to the proton channel in the F0 part of the ATP synthase.
Journal of Biological ChemistryNucleotide-dependent Movement of the ε Subunit between α and β Subunits in the Escherichia coli F1F0-type ATPase
100 Citations1996Robert Aggeler, Roderick Capaldi
Mutants of ECF1-ATPase were generated, containing cysteine residues in one or more of the following positions: αSer-411, βGlu-381, and εSer-108, after which disulfide bridges could be created by CuCl2 induced oxidation in high yield between α and α, β and β, γ and γ, α and δ, and α and β.
BiochemistryIntroduction of reactive cysteine residues in the .epsilon. subunit of Escherichia coli F1 ATPase, modification of these sites with (azidotetrafluorophenyl)maleimides, and examination of changes in the binding of the .epsilon. subunit when different nucleotides are in catalytic sites
98 Citations1992Robert Aggeler, Kathy Chicas-Cruz +3 more
Two mutants and wild-type enzyme were reacted with NEM to examine the solvent accessibility of Cys residues and with novel photoactivated cross-linkers, tetrafluorophenyl azide-maleimides (TFPAM's), to examine near-neighbor relationships of subunits.
Proceedings of the National Academy of SciencesFunctional and idling rotatory motion within F <sub>1</sub> -ATPase
80 Citations1997D. Sabbert, Siegfried Engelbrecht +1 more
The observed relaxation of the absorption anisotropy is fully compatible with a unidirectional and stepping rotation of gamma over three equidistantly spaced angular positions in the hexagon formed by the alternating subunits alpha and beta.
BiochemistryThe ATPase Inhibitor Protein from Bovine Heart Mitochondria: The Minimal Inhibitory Sequence
76 Citations1996Mark J. van Raaij, George L. Orriss +5 more
The mitochondrial ATPase inhibitor subunit is a basic protein of 84 amino acids that helps to regulate the activity of F1F0-ATPase and appears to have a mainly random coil structure in solution, but smaller inhibitory fragments can adopt the correct inhibitory conformation when they from a complex with the ATPase.
FEBS LettersObservations of rotation within the F<sub>o</sub>F<sub>1</sub>‐ATP synthase: deciding between rotation of the F<sub>o</sub><i>c</i> subunit ring and artifact
73 Citations2000Satoshi P. Tsunoda, Robert Aggeler +4 more
It is found that detergents which adequately disperse the enzyme for the rotation assay also tend to transform FoF1‐ATP synthase into an Fo inhibitor‐insensitive state in which F1 can hydrolyze ATP regardless of the state of the Fo.
FEBS LettersATP synthase: constrained stoichiometry of the transmembrane rotor
71 Citations2001Daniel J. Müller, Norbert A. Dencher +7 more
Atomic force microscopy allowed individual subunits of the cylindrical transmembrane rotors from spinach chloroplast and from Ilyobacter tartaricus ATP synthase to be directly visualized in their native‐like environment and suggested the rotor diameter and stoichiometry to be determined by the shape of the subunits and their nearest neighbor interactions.
Journal of Bioenergetics and BiomembranesStoichiometry of Energy Coupling by Proton-Translocating ATPases: A History of Variability
69 Citations2000John J. Tomashek, W S Brusilow
Recent discoveries concerning the structure of the ATPases, their assembly and the stoichiometry of their numerous subunits, particularly the proton-carrying proteolipid (subunit c) of the FO and V0 sectors, have shed new light on this question and raise the possibility of variable coupling ratios modulated by variable proteolIPid stoichiometries.
Journal of Biological ChemistryLengthening the Second Stalk of F1F0 ATP Synthase in Escherichia coli
65 Citations1999Paul L. Sorgen, M Bubb +1 more
The results of both insertion and deletion experiments support a model in which the second stalk is a flexible feature of the enzyme rather than a rigid rod-like structure.
Proceedings of the National Academy of SciencesEnergy-driven subunit rotation at the interface between subunit a and the c oligomer in the F <sub>O</sub> sector of <i>Escherichia coli</i> ATP synthase
64 Citations2001Marcus L. Hutcheon, T. Michael Duncan +2 more
Evidence is reported for an energy-dependent rotation of the c ring relative to subunit a at a rotor/stator interface between the oligomeric ring of c subunits and the single-copy a subunit (stator).
Journal of Biological ChemistryThe Conformation of the ε- and γ-Subunits within theEscherichia coli F1 ATPase
56 Citations2001Andrew C. Hausrath, Roderick Capaldi +1 more
It is shown that the map of the F1 complex is consistent with the structure of the isolated subunits, and it is argued that these large-scale changes in conformation reflect distinct functional states that occur during the rotation of the γ-subunit within the α3β3 hexamer.
Journal of Bioenergetics and BiomembranesMutagenic Analysis of the F 0 Stator Subunits
56 Citations2000Brian Cain
These approaches were used to demonstrate that the a subunit in association with the ring of c subunits houses the proton channel through F1F0-ATP synthase.
Journal of Bioenergetics and BiomembranesWhy Is the Mechanical Efficiency of F1-ATPase So High?
54 Citations2000George Oster, Hongyun Wang
The experimentally measured mechanical efficiency of the F1-ATPase under viscous loading is nearly 100%, far higher than any other hydrolysis-driven molecular motor.
Biological Chemistry Hoppe-SeylerAsymmetry and Structural Changes in ECF Examined by Cryoelectronmicroscopy
52 Citations1994Stephan Wilkens, Roderick Capaldi
Journal of Biological ChemistryThe γε-c Subunit Interface in the ATP Synthase ofEscherichia coli
38 Citations1999Birte Schulenberg, Robert Aggeler +2 more
Results for epsilonE31C/cc'Q42C indicate that the c subunit ring rotates with the central stalk element, which argues for a gammaepsilon-c subunit rotor.
BiochemistryNew Probes of the F<sub>1</sub>-ATPase Catalytic Transition State Reveal That Two of the Three Catalytic Sites Can Assume a Transition State Conformation Simultaneously
36 Citations2000Sashi Nadanaciva, Joachim Weber +1 more
MgADP in combination with fluoroscandium (ScFx) is shown to form a potently inhibitory, tightly bound, noncovalent complex at the catalytic sites of F(1)-ATPase, and it is demonstrated that two sites have the capability to form the transition state simultaneously.
BiochemistryA Triple Mutation in the a Subunit of the<i>Escherichia</i><i>coli/Propionigenium</i><i>modestum</i>F<sub>1</sub>F<sub>o</sub>ATPase Hybrid Causes a Switch from Na<sup>+</sup>Stimulation to Na<sup>+</sup>Inhibition
33 Citations1998Georg Kaim, Peter Dimroth
Results show for the first time that the coupling ion selectivity of F1Fo ATPases is determined by structural elements not only of the c subunit but also of the a subunit.
Biochimica et Biophysica Acta (BBA) - BioenergeticsThe ϵ subunit of bacterial and chloroplast F1F0 ATPases
31 Citations2000Roderick Capaldi, Birte Schulenberg
Biochimica et Biophysica Acta (BBA) - BioenergeticsEffect of disulfide cross-linking between α and δ subunits on the properties of the F1 adenosine triphosphatase of Escherichia coli
31 Citations1986Philip D. Bragg, Cynthia Hou
BiochemistryATP binding causes a conformational change in the .gamma. subunit of the Escherichia coli F1ATPase which is reversed on bond cleavage
29 Citations1994Paola Turina, Roderick Capaldi
The results indicate that ATP or ATP gamma S binding causes the fluorescence enhancement of CM bound to the gamma subunit and that this conformational change is reversed upon bond cleavage to yield ADP.
Journal of Bioenergetics and BiomembranesThe Oligomeric Subunit c Rotor in the Fo Sector of ATP Synthase: Unresolved Questions in Our Understanding of Function
21 Citations2000Robert Fillingame, Weiping Jiang +1 more
A model for the oligomeric c-rotor of the Fo sector of ATP synthase and its interaction with subunit a during H+-transport driven rotation, based upon the solution structure of monomeric subunit c, determined by NMR, provides a useful framework for addressing questions raised by other experiments.
Journal of Bioenergetics and BiomembranesNotes on the Mechanism of ATP Synthesis
15 Citations2000Mario A. Bianchet, Peter L. Pedersen +1 more
The most commonly quoted mechanism of the coupling between the electrochemical proton gradient and the formation of ATP from ADP and Pi assumes that all states of the F1 portion of the ATP synthase have β subunits in “tight,’ “loose,” and “open” conformations.
Journal of Bioenergetics and BiomembranesThe Catalytic Transition State in ATP Synthase
15 Citations2000Alan E. Senior, Joachim Weber +1 more
It is speculated that formation and collapse of the transition state may engender catalytic site α/β subunit-interface conformational movement, which is linked to γ-subunit rotation, as well as mutations of critical catalytic residues to determine side-chain ligands required to stabilize the Transition state.
Journal of Bioenergetics and BiomembranesOsmomechanics of the Propionigenium modestum Fo Motor
4 Citations2000Peter Dimroth, Ulrich Matthey +1 more
This work proposes a catalytic mechanism for torque generation by the Fo motor that is in accord with all experimental data and is in quantitative agreement with the requirement for ATP synthesis.