The evolution of A-, F-, and V-type ATP synthases and ATPases: reversals in function and changes in the H+/ATP coupling ratio

FEBS Lett. 2004 Oct 8;576(1-2):1-4. doi: 10.1016/j.febslet.2004.08.065.


Members of the FoF1, AoA1 and VoV1 family of ATP synthases and ATPases have undergone at least two reversals in primary function. The first was from a progenitor proton-pumping ATPase to a proton-driven ATP synthase. The second involved transforming the synthase back into a proton-pumping ATPase. As proposed earlier [FEBS Lett. 259 (1990) 227], these reversals required changes in the H+/ATP coupling ratio from an optimal value of about 2 for an ATPase function to about 4 for an ATP synthase function. The doubling of the ratio that occurred at the ATPase-to-Synthase transition was accomplished by duplicating the gene that encodes the nucleotide-binding catalytic subunits followed by loss of function in one of the genes. The halving of the ratio that occurred at the Synthase-to-ATPase transition was achieved by a duplication/fusion of the gene that encodes the proton-binding transporter subunits, followed by a loss of function in one half of the double-sized protein. These events allowed conservation of quaternary structure, while maintaining a sufficient driving force to sustain an adequate phosphorylation potential or electrochemical gradient. Here, we describe intermediate evolutionary steps and a fine-tuning of the H+/ATP coupling ratio to optimize synthase function in response to different environments. In addition, we propose a third reversal of function, from an ATPase back to an ATP synthase. In contrast to the first two reversals which required a partial loss in function, the change in coupling ratio required for the third reversal is explained by a gain in function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Base Sequence / genetics
  • Catalytic Domain
  • Escherichia coli / enzymology
  • Evolution, Molecular*
  • Gene Duplication
  • H(+)-K(+)-Exchanging ATPase / chemistry*
  • Humans
  • Models, Biological
  • Protein Structure, Quaternary
  • Proton-Translocating ATPases / chemistry*
  • Proton-Translocating ATPases / genetics
  • Proton-Translocating ATPases / metabolism*
  • Protons


  • Protons
  • Adenosine Triphosphatases
  • H(+)-K(+)-Exchanging ATPase
  • Proton-Translocating ATPases