Coupling H+ transport and ATP synthesis in F1F0-ATP synthases: glimpses of interacting parts in a dynamic molecular machine.
Reversible, F1F0-type ATPases (also termed F-ATP synthases) catalyze the synthesis of ATP during oxidative phosphorylation. In animal cells, the enzyme traverses the inner mitochondrial membrane and uses the energy of an H+ electrochemical gradient, generated by electron transport, in coupling H+ translocation to ATP formation. Closely related enzymes are found in the plasma membrane of bacteria such as Escherichia coli, where the enzymes function reversibly depending upon nutritional circumstance. The F1F0-type enzymes are more distantly related to a second family of H(+)-translocating ATPases, the vacuolar-type or V-ATPases. Recent structural information has provided important hints as to how these enzymes couple H+ transport to the chemical work of ATP synthesis. The simplest F1F0-type enzymes, e.g. as in E. coli, are composed of eight types of subunits in an unusual stoichiometry of alpha 3 beta 3 gamma delta epsilon (F1) and a1b2c12 (F0). F1 extends from the membrane, with the alpha and beta subunits alternating around a central subunit gamma. ATP synthesis occurs alternately in different beta subunits, the cooperative tight binding of ADP + Pi at one catalytic site being coupled to ATP release at a second. The differences in binding affinities appear to be caused by rotation of the gamma subunit in the center of the alpha 3 beta 3 hexamer. The gamma subunit traverses a 4.5 nm stalk connecting the catalytic subunits to the membrane-traversing F0 sector. Subunit c is the H(+)-translocating subunit of F0. Protonation/deprotonation of Asp61 in the center of the membrane is coupled to structural changes in an extramembranous loop of subunit c which interacts with both the gamma and epsilon subunits. Subunits gamma and epsilon appear to move from one subunit c to another as ATP is synthesized. The torque of such movement is proposed to cause the rotation of gamma within the alpha 3 beta 3 complex. Four protons are translocated for each ATP synthesized. The movement of gamma and epsilon therefore probably involves a unit of four c subunits. The organization of subunits in F0 remains a mystery; it will have to be understood if we are to understand the mechanism of torque generation.
Fillingame
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Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison 53706, USA. filingam@macc.wisc.edu
D000251:Adenosine Triphosphatases; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D002417:Cattle; D004734:Energy Metabolism; D004926:Escherichia coli / Q000201:enzymology; D006089:Gram-Negative Anaerobic Bacteria / Q000201:enzymology; D008929:Mitochondria, Heart / Q000201:enzymology; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017494:Proton Pumps / Q000378:metabolism*; D018892:Proton-Motive Force; D006180:Proton-Translocating ATPases / Q000737:chemistry* / Q000378:metabolism; D012399:Rotation; D013329:Structure-Activity Relationship; D019415:Torque
D001426:Bacterial Proteins; D017494:Proton Pumps; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D006180:Proton-Translocating ATPases