Nilmadhab Chakrabarti, Emad Tajkhorshid, Benoît Roux, and Régis
Pomès.
Molecular basis of proton blockage in aquaporins.
Structure, 12:65-74, 2004.
CHAK2004-ET
Water transport channels in membrane proteins of the aquaporin superfamily are impermeable to ions, including H+ andOH-. 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 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 are opposed by the electrostatic field of the channel.
