High-resolution structure and mechanism of an F/V-hybrid rotor ring in a Na⁺-coupled ATP synthase

Nat Commun. 2014 Nov 10;5:5286. doi: 10.1038/ncomms6286.


All rotary ATPases catalyse the interconversion of ATP and ADP-Pi through a mechanism that is coupled to the transmembrane flow of H(+) or Na(+). Physiologically, however, F/A-type enzymes specialize in ATP synthesis driven by downhill ion diffusion, while eukaryotic V-type ATPases function as ion pumps. To begin to rationalize the molecular basis for this functional differentiation, we solved the crystal structure of the Na(+)-driven membrane rotor of the Acetobacterium woodii ATP synthase, at 2.1 Å resolution. Unlike known structures, this rotor ring is a 9:1 heteromer of F- and V-type c-subunits and therefore features a hybrid configuration of ion-binding sites along its circumference. Molecular and kinetic simulations are used to dissect the mechanisms of Na(+) recognition and rotation of this c-ring, and to explain the functional implications of the V-type c-subunit. These structural and mechanistic insights indicate an evolutionary path between synthases and pumps involving adaptations in the rotor ring.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Synthetase Complexes / chemistry*
  • ATP Synthetase Complexes / physiology*
  • Acetobacterium / enzymology*
  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / metabolism
  • Crystallization
  • Hydrogen / metabolism
  • Microscopy, Atomic Force
  • Models, Biological
  • Molecular Dynamics Simulation
  • Protein Subunits / chemistry*
  • Protein Subunits / physiology*
  • Sodium / metabolism


  • Protein Subunits
  • Adenosine Diphosphate
  • Hydrogen
  • Adenosine Triphosphate
  • Sodium
  • ATP Synthetase Complexes

Associated data

  • PDB/4BEM