Molecular basis of proton blockage in aquaporins.
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.
Chakrabarti
Nilmadhab
N
Structural Biology and Biochemistry, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Tajkhorshid
Emad
E
Roux
Benoît
B
Pomès
Régis
R
D020346:Aquaporins / Q000737:chemistry* / Q000235:genetics; D001692:Biological Transport / Q000502:physiology; D003198:Computer Simulation; D006859:Hydrogen / Q000737:chemistry; D006860:Hydrogen Bonding; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry*; D011522:Protons; D055672:Static Electricity; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry*
D020346:Aquaporins; D007473:Ion Channels; D011522:Protons; D014867:Water; D006859:Hydrogen; D010100:Oxygen