Functional rotation induced by alternating protonation states in the multidrug transporter AcrB: all-atom molecular dynamics simulations

Biochemistry. 2013 Oct 29;52(43):7648-58. doi: 10.1021/bi400119v. Epub 2013 Oct 18.


The multidrug transporter AcrB actively exports a wide variety of noxious compounds using proton-motive force as an energy source in Gram-negative bacteria. AcrB adopts an asymmetric structure comprising three protomers with different conformations that are sequentially converted during drug export; these cyclic conformational changes during drug export are referred to as functional rotation. To investigate functional rotation driven by proton-motive force, all-atom molecular dynamics simulations were performed. Using different protonation states for the titratable residues in the middle of the transmembrane domain, our simulations revealed the correlation between the specific protonation states and the side-chain configurations. Changing the protonation state for Asp408 induced a spontaneous structural transition, which suggests that the proton translocation stoichiometry may be one proton per functional rotation cycle. Furthermore, our simulations demonstrate that alternating the protonation states in the transmembrane domain induces functional rotation in the porter domain, which is primarily responsible for drug transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartic Acid / chemistry
  • Databases, Protein
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism
  • Models, Molecular*
  • Molecular Dynamics Simulation
  • Multidrug Resistance-Associated Proteins / chemistry*
  • Multidrug Resistance-Associated Proteins / metabolism
  • Phosphatidylethanolamines / chemistry
  • Phosphatidylethanolamines / metabolism
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Proton-Motive Force
  • Protons


  • AcrB protein, E coli
  • Escherichia coli Proteins
  • Lipid Bilayers
  • Multidrug Resistance-Associated Proteins
  • Phosphatidylethanolamines
  • Protein Subunits
  • Protons
  • 1-palmitoyl-2-oleoylphosphatidylethanolamine
  • Aspartic Acid