On the question of hydronium binding to ATP-synthase membrane rotors

Biophys J. 2010 Oct 6;99(7):L53-5. doi: 10.1016/j.bpj.2010.07.046.

Abstract

A recently determined atomic structure of an H(+)-coupled ATP-synthase membrane rotor has revived the long-standing question of whether protons may be bound to these structures in the form of a hydronium ion. Using both classical and quantum-mechanical simulations, we show that this notion is implausible. Ab initio molecular dynamics simulations of the binding site demonstrate that the putative H(3)O(+) deprotonates within femtoseconds. The bound proton is thus transferred irreversibly to the carboxylate side chain found in the ion-binding sites of all ATP-synthase rotors. This result is consistent with classical simulations of the rotor in a phospholipid membrane, on the 100-nanosecond timescale. These simulations show that the hydrogen-bond network seen in the crystal structure is incompatible with a bound hydronium. The observed coordination geometry is shown to correspond instead to a protonated carboxylate and a bound water molecule. In conclusion, this study underscores the notion that binding and transient storage of protons in the membrane rotors of ATP synthases occur through a common chemical mechanism, namely carboxylate protonation.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus / enzymology*
  • Binding Sites
  • Cell Membrane / metabolism*
  • Computer Simulation
  • Crystallography, X-Ray
  • Models, Biological
  • Molecular Motor Proteins / chemistry
  • Molecular Motor Proteins / metabolism*
  • Onium Compounds / metabolism*
  • Proton-Translocating ATPases / metabolism*
  • Protons

Substances

  • Molecular Motor Proteins
  • Onium Compounds
  • Protons
  • hydronium ion
  • Proton-Translocating ATPases