Metabolomics

ATP Synthase

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In 1997 the Nobel Prize in chemistry was awarded to Professor Paul D. Boyer, University of California, Los Angeles, USA, and Dr. John E. Walker, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom for their elucidation of the mechanism of ATP synthase. Dr. Nicholson, the IUBMB and Sigma-Aldrich are proud to begin our metabolic pathways animation series with an interpretation of the ATP synthase molecular machine.



ATP Synthase
an interpretation by
Donald Nicholson

This is the all-important reaction in which the proton-motive force, produced by proton translocation, is coupled to the synthesis of ATP from ADP and phosphate. ATP Synthase is a complex structure consisting of two domains Fo and F1. F1 is a spherical structure, which, in the case of mitochondria, sticks out into the matrix and is anchored to the membrane by a stator to prevent rotation. It consists of three α- and three β- subunits, all of which can bind nucleotides, but only the β-subunits can take part in the reactions. Fo is a cylindrical structure capable of rotation when driven by translocated protons and is linked to a central stalk that can revolve inside F1.

The mechanism that drives ATP synthesis seems to depend upon a binding charge conception in which catalytic sites on the β-subunits have different affinities for nucleotides and are designated loose (L), tight (T), and open (O). In the animation these are colored pink, blue, and green, respectively. The loose (L) sites bind the substrates (ADP and phosphate) reversibly. The T sites then bind the reactants so tightly that ATP is formed. The O sites, which have a low affinity for substrates, then release the ATP already formed in the T state. The central stalk is driven by the retro-location of protons through Fo (counter-clockwise as seen from above), and rotates in 120° stages. At each stage each of the β-subunits in turn change conformation: L changes to T (after binding ADP and phosphate), T to O, and O to L (after releasing ATP). The new L site then binds new ADP and phosphate and begins a new reaction sequence. One complete revolution of Fo therefore results in the formation of 3 ATP, one from each of the β-subunits. In this example, about 10 protons need to be retro-located for each complete revolution of Fo, which means that the formation of 1 ATP requires about 3.3 protons, though other species may be different. ATP synthase is thought to revolve at more than 100Hz (revolutions/sec.), which is sufficient to produce a turnover equivalent to the weight of our body in ATP each day.


References

  1. Boyer, P.D., The binding change mechanism for ATP synthase - Some probabilities and possibilities, Biochimica et Biophysica Acta, 1140, 215-250 (1993).
  2. Abrahams, J.P., Leslie, A.G., Lutter, R., and Walker J.E., Structure at 2.8 Å resolution of F1 -ATPase from bovine heart mitochondria, Nature, 370, 621-628 (1994).
  3. Boyer, P.D., The ATP synthase - a splendid molecular machine, Annual Review in Biochemistry, 66, 717-749 (1997).
  4. Gibbons, C., Montgomery, M.G., Leslie, A.G.W. & Walker, J.E. The structure of the central stalk in bovine F1-ATPase at 2.4 Å resolution. Nature Struct. Biol., 7, 1055-1061 (2000).
  5. Cabezon, E., Arrechaga, I., Butler, P.J.G. & Walker, J.E. Dimerization of bovine F1-ATPase by binding the inhibitor protein, IF1. J. Biol. Chem., 275, 28353-28355 (2000).
  6. Cabezon, E., Butler, P.J., Runswick, M.J. & Walker J.E. Modulation of the oligomerization state of the bovine F1-ATPase inhibitor protein, IF1, by pH. J. Biol. Chem., 275, 25460-25464.
  7. Stock, D., Leslie, A.G.W., Walker, J.E. Molecular architecture of the rotary motor in ATP synthase. Science, 286, 1700-1705 (1999).
  8. Karrasch, S., Walker, J.E. Novel features in the structure of bovine ATP synthase. J. Mol. Biol., 290, 379-384 (1999).
  9. >Orriss, G.L., Leslie, A.G.W., Braig, K., Walker, J.E. Bovine F1-ATPase covalently inhibited with 4-chloro-7-nitrobenzofurazan: the structure provides further support for a rotary catalytic mechanism. Structure, 6, 831-837 (1998).

 

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