Microscopic rotary mechanism of ion translocation in the F(o) complex of ATP synthases

Nat Chem Biol. 2010 Dec;6(12):891-9. doi: 10.1038/nchembio.457. Epub 2010 Oct 24.


The microscopic mechanism of coupled c-ring rotation and ion translocation in F(1)F(o)-ATP synthases is unknown. Here we present conclusive evidence supporting the notion that the ability of c-rings to rotate within the F(o) complex derives from the interplay between the ion-binding sites and their nonhomogenous microenvironment. This evidence rests on three atomic structures of the c(15) rotor from crystals grown at low pH, soaked at high pH and, after N,N'-dicyclohexylcarbodiimide (DCCD) modification, resolved at 1.8, 3.0 and 2.2 Å, respectively. Alongside a quantitative DCCD-labeling assay and free-energy molecular dynamics calculations, these data demonstrate how the thermodynamic stability of the so-called proton-locked state is maximized by the lipid membrane. By contrast, a hydrophilic environment at the a-subunit-c-ring interface appears to unlock the binding-site conformation and promotes proton exchange with the surrounding solution. Rotation thus occurs as c-subunits stochastically alternate between these environments, directionally biased by the electrochemical transmembrane gradient.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Crystallization
  • Dicyclohexylcarbodiimide / chemistry
  • Energy Metabolism / physiology
  • Hydrogen-Ion Concentration
  • Ions / metabolism
  • Membrane Lipids / chemistry
  • Models, Molecular
  • Molecular Motor Proteins / chemistry
  • Molecular Motor Proteins / metabolism
  • Protein Conformation
  • Proton-Translocating ATPases / metabolism*
  • Protons
  • Spectrometry, Mass, Electrospray Ionization
  • Spirulina / chemistry
  • Thermodynamics
  • X-Ray Diffraction


  • Ions
  • Membrane Lipids
  • Molecular Motor Proteins
  • Protons
  • Dicyclohexylcarbodiimide
  • Proton-Translocating ATPases

Associated data

  • PDB/2XQS
  • PDB/2XQT
  • PDB/2XQU