Molecular basis of proton blockage in aquaporins

Structure. 2004 Jan;12(1):65-74. doi: 10.1016/j.str.2003.11.017.

Abstract

Water transport channels in membrane proteins of the aquaporin superfamily are impermeable to ions, including H+ and OH-. We examine the molecular basis for the blockage of proton translocation through the single-file water chain in the pore of a bacterial aquaporin, GlpF. We compute the reversible thermodynamic work for the two complementary steps of the Grotthuss "hop-and-turn" relay mechanism: consecutive transfers of H+ along the hydrogen-bonded chain (hop) and conformational reorganization of the chain (turn). In the absence of H+, the strong preference for the bipolar orientation of water around the two Asn-Pro-Ala (NPA) motifs lining the pore over both unidirectional polarization states of the chain precludes the reorganization of the hydrogen-bonded network. Inversely, translocation of an excess proton in either direction is opposed by a free-energy barrier centered at the NPA region. Both hop and turn steps of proton translocation are opposed by the electrostatic field of the channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aquaporins / chemistry*
  • Aquaporins / genetics
  • Biological Transport / physiology
  • Computer Simulation
  • Hydrogen / chemistry
  • Hydrogen Bonding
  • Ion Channels / chemistry*
  • Ion Channels / genetics
  • Models, Molecular
  • Oxygen / chemistry*
  • Protons*
  • Static Electricity
  • Structure-Activity Relationship
  • Water / chemistry*

Substances

  • Aquaporins
  • Ion Channels
  • Protons
  • Water
  • Hydrogen
  • Oxygen