Why protons don't go through 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. 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. Notably, the 10-12-kcal-per-mole barrier to proton translocation peaking at the NPA region results from a combination of factors. These include not only the orientational control of water molecules but also desolvation penalties and electrostatic effects caused by the charge distribution in the channel.

N. CHAKRABARTI, E. TAJKHORSHID, B. ROUX and R. POMES. "Molecular Basis of Proton Blockage in Aquaporins" Structure 12, 65-74 (2004). [ PubMed ]

C&E News by Amanda Yarnell, "Blockade in the cell's waterway"

More on proton wires...

R. POMES and B. ROUX, "Quantum Effects on the Structure and Energy of a Protonated Linear Chain of Hydrogen-Bonded Water Molecules", Chem. Phys. Lett. 234, 416-624 (1995). [ pdf ]

R. POMES and B. ROUX, "Theoretical Study of H+ Translocation along a Model Proton Wire", J. Phys. Chem. 100, 2519-2527 (1996).

R. POMES and B. ROUX, "Structure and Dynamics of a Proton Wire: A Theoretical Study of H+ Translocation along the Single-File Water Chain in the Gramicidin A Channel", Biophys. J. 71, 19-39 (1996).

R. POMES and B. ROUX, "Free energy profiles for H+ conduction along hydrogen-bonded chains of water molecules", Biophys. J. 75, 33-40 (1998). [ pdf ]

M.F. SCHUMAKER, R. POMES and B. ROUX, "A combined molecular dynamics diffusion model of single proton conduction through gramicidin", Biophys. J. 79, 2840-2857 (2000). [ pdf ]

M.F. SCHUMAKER, R. POMES and B. ROUX, "Framework Model for Single Proton Conduction Through Gramicidin", Biophys. J. 80, 12-30 (2001). [ pdf ]

R. POMES and B. ROUX, "Molecular Mechanism of H+ Conduction in the Single-File Water Chain of the Gramicidin Channel", Biophys. J. 82, 2304-2316 (2002). [ pdf ]