The Unfolding of a Catalytic Mechanism for the Remarkable ATP Synthase

  • Teri Mélèse
Part of the NATO ASI Series book series (NSSA, volume 91)


In the past two decades, investigators in the field of bioenergetics have shown that a particular multisubunit protein complex (the ATP synthase) on the inner membrane of mitochondria, and on plant and bacterial membranes uses the energy supplied by an electrochemical or pH gradient to drive the net synthesis of ATP (see Figure 1). This energy could exert its effect either indirectly through a physical change in the structure of the protein itself (i.e. a conformational change) which would facilitate changes at the catalytic site, or directly, by the active donation of protons into the catalytic site which would be used in the covalent bond step when ATP is formed from ADP and Pi. Mitchell (1974, 1978) has suggested that effective removal of an oxygen group from Pi could be accomplished by such protonations at the catalytic site. However, over the past 10 years, increasing evidence has accrued showing that the energy provided by electron transport down the respiratory chain is used indirectly for the phosphorylation of ADP by Pi.


Oxidative Phosphorylation Catalytic Subunit Catalytic Site Succinic Anhydride Submitochondrial Particle 
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  1. Abbot, M.S., Czarnecki, J.J., and Selman, B.R. 1984, Localization of the high affinity binding site for ATP on the membrane bound chloroplast ATP synthase, J. Biol. Chem. 259: 12271.Google Scholar
  2. Baird, B.A., and Hammes, G.G. 1979, Structure of oxidative and photophosphorylation coupling factor complexes, Biochim. Biophys. Acta 549: 31.Google Scholar
  3. Binder A., Jagendorf, A., and Ngo E. 1978, Isolation and composition of the subunits of spinach chloroplast coupling factor protein, J. Biol. Chem. 253: 3094.Google Scholar
  4. Boyer, P.D. 1983, How cells make ATP, In: Biochemistry of Metabolic Processes, ed. F.W. Stratman et al., pp 465–477, Elsevier, New York.Google Scholar
  5. Boyer, P.D., Cross, R.L. and Momsen, W. 1973, A new concept for energy coupling in oxidative phosphorylation based on a molecular explanation of the oxygen exchange reactions, Proc. Nat’l. Acad. Sci. USA 70: 2837–2839.Google Scholar
  6. Boyer, P.D., Smith, D.J., Rosing, J., and Kayalar, C. 1975, Bound nucleotides and conformational changes in oxidative and photophosphorylation, In: Electron Transfer Chains and Oxidative Phosphorylation, ed. E. Quagliariello, et. al., pp. 361–72, Amsterdam: North Holland.Google Scholar
  7. Chernyak, B.C., and Kozlov, I.A. 1979, Adenylylimidodiphosphate release from the active site of submitochondrial particles ATPase, FEBS Lett. 104: 215.PubMedCrossRefGoogle Scholar
  8. Choate, G.L., Hutton, R.L., and Boyer, P.D. 1979, Occurrence and significance of oxygen exchange reactions catalyzed by mitochondrial adenosine triphosphatase preparations, J. Biol. Chem. 254: 286.Google Scholar
  9. Cohn, M. 1953, A study of oxidative phosphorylation with 018-labeled inorganic phosphate. J. Bio. Chem. 201: 735.Google Scholar
  10. Cross, R.L., 1981, The mechanism and regulation of ATP synthesis by F1-ATPases, Ann. Rev. Biochem. 50: 681.Google Scholar
  11. Cross, R.L., and Kohlbrenner, W.E. 1978, The mode of inhibition of oxidative phosphorylation by efrapeptin (A23871), J. Biol. Chem. 253: 4865.Google Scholar
  12. Doetsch, R.N., and Sjoblad, R.D. 1980, Flagellar structure and function in Eubacteria, Ann. Rev. Microbiol. 34: 69.Google Scholar
  13. Feldman, R.I., and Sigman, D. 1982, The synthesis of enzyme-bound ATP by soluble chloroplast coupling Factor 1, J. Biol. Chem. 257: 1676.Google Scholar
  14. Ferguson, S.J., Lloyd, W.J., and Radda, G.K. 1975, The mitochondrial ATPase: Selective modification of a nitrogen residue on the subunit, Eur. J. Biochem. 54: 127.Google Scholar
  15. Gresser, M.J., Cardon, J., Rosen, G., and Boyer, P.D. 1979, Demonstration and quantitation of catalytic and noncatalytic bound ATP in submitochondrial particles during oxidative phosphorylation, J. Biol. Chem. 254: 10649.Google Scholar
  16. Gresser, M.J., Meyers, J.A., and Boyer, P.D. 1982, Catalytic site cooperativity of beef heart mitochondrial F1 adenosine triphosphatase: Correlations of initial velocity, bound intermediates and oxygen exchange measurements with an alternating three-site model, J. Biol. Chem.Google Scholar
  17. Hackney, D.D., and Boyer, P.D. 1978, Evaluation of the partitioning of bound Pi during medium and intermediate Pi HOH oxygen exchange reactions of yeast inorganic pyrophosphatase, J. Biol. Chem. 254: 1164.Google Scholar
  18. Hirota, N., and Imae, Y. 1983, Na+-driven flagellar motors of an alkalophilic bacillus strain YN-1, J. Biol. Chem. 258: 10577.Google Scholar
  19. Hutton, R.L., and Boyer, P.D. 1979, Subunit interaction during catalysis: Alternating site cooperativity of mitochondrial adenosine triphosphatase, J. Biol. Chem. 254: 9990.Google Scholar
  20. Jagendorf, A.T. 1975, Chloroplast membranes and coupling factor conformations, Fed. Proc. 34: 1718.Google Scholar
  21. Kayalar, C., Rosing, J., and Boyer, P.D. 1977, An alternating site sequence for oxidative phosphorylation suggested by measurement of substrate binding patterns and exchange reaction inhibitions, J. Biol. Chem. 252: 2486.Google Scholar
  22. Kohlbrenner, W.E., and Cross, R.L. 1978, Efrapeptin prevents modification by phenylglyoxal of an essential arginyl residue in mitochondrial adenosine triphosphatase, J. Biol. Chem. 253: 7609.Google Scholar
  23. Merchant S., Shaner, S. and Selman, B.A. 1983, Molecular weight and subunit stoichiometry of the chloroplast coupling Factor 1 from Chamydomonas reinhardi, J. Biol. Chem. 258: 1026.Google Scholar
  24. Mitchell, P. 1974, A chemiosmotic molecular mechanism for proton translocating adenosine triphosphatases, FEBS Lett. 43: 189.PubMedCrossRefGoogle Scholar
  25. Mitchell, P. 1979, Keilin’s respiratory chain concept and its chemiosmotic consequences, Science 206: 1148.PubMedCrossRefGoogle Scholar
  26. Mitchell, R.A., Hill, R.D. and Boyer, P.D. 1967, Mechanistic implications of Mg++ and adenine nucleotide requirements for energy-linked reations catalyzed by mitochondrial particles, J. Biol. Chem. 242: 1793.Google Scholar
  27. Moroney, J.V., Lopresti, L., McEwen, B.F., McCarty, R.E., and Hammes, G.G. 1983, The Mr-value of chloroplast coupling factor 1, FEBS Lett. 158: 58.CrossRefGoogle Scholar
  28. Nageswara Rao, B.D., Kayne, F., and Cohn, M. 1979, 31P NMR studies of enzyme-bound substrates of rabbit muscle, J. Biol. Chem. 254: 2689.Google Scholar
  29. Nalin, C.M., and Cross, R.L. 1980, Cooperativity between adenine nucleotide binding sites on mitochondrial F1 ATPase, Fed. Proc. 39: 1843.Google Scholar
  30. O’Farrell, P.H. 1975, High resolution two-dimensional electro-phoresis of proteins, J. Biol. Chem. 250: 4007.Google Scholar
  31. Penefsky, H.S. 1979, Mitochondrial ATPase, Adv. Enzymol. 49: 223.Google Scholar
  32. Rosen, G., Gresser, M.J., Vinkler, C., and Boyer, P.D. 1979, Assessment of total catalytic sites and the nature of bound nucleotide participation in photophosphorylation, J. Biol. Chem. 254: 10654.Google Scholar
  33. Rosing, J., Kayalar, C. and Boyer, P.D. 1977, Evidence for energy-dependent change in phosphate binding for mitochondrial oxidative phosphorylation based on measurement of medium and intermediate phosphate-water exchanges, J. Biol. Chem. 252: 2478.Google Scholar
  34. Satre, M., Lunardi, J., Pougeois, R., and Vignais, P.V. 1979, Inactivation of Escherichia coli BF1-ATPase by dicyclohexylcarbodiimide chemical modification of the subunit, Biochem. 18: 3134.CrossRefGoogle Scholar
  35. Senior, A.E., Langman, L., Cox, G.B., and Gibson, F. 1983, Oxidative phosphorylation in Escherichia coli, Biochem. J. 210: 395.Google Scholar
  36. Senior, A.E., and Wise, J.G. 1983, Proton ATPase of E. coli and mitochondria, J. Memb. Biol. 73: 105.Google Scholar
  37. Silverman, M., and Simon, M. 1974, Flagellar rotation and the mechanism of bacterial motility, Nature 249: 73.PubMedCrossRefGoogle Scholar
  38. Younis, H.M., Winget, G.D., and Racker, E. 1977, Requirement of the S subunit of chloroplast coupling factor 1 for photophosphorylation, J. Biol. Chem. 252: 1814.Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Teri Mélèse
    • 1
  1. 1.Department of Chemistry and BiochemistryUniversity of CaliforniaLos AngelesUSA

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