TY - JOUR
T1 - Molecular Basis of Proton Blockage in Aquaporins
AU - Chakrabarti, Nilmadhab
AU - Tajkhorshid, Emad
AU - Roux, Benoît
AU - Pomès, Régis
N1 - Funding Information:
We thank Klaus Schulten and Wonpil Im for useful discussions. We gratefully acknowledge the Canadian Institutes of Health Research (operating grant MOP43949) and the Ontario Centre for Genomics Computing for support. R.P. is a CRCP Chairholder.
PY - 2004/1
Y1 - 2004/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.str.2003.11.017
DO - 10.1016/j.str.2003.11.017
M3 - Article
C2 - 14725766
AN - SCOPUS:1642493669
VL - 12
SP - 65
EP - 74
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 1
ER -