Morten Ø. Jensen, Emad Tajkhorshid, and Klaus Schulten.
Electrostatic tuning of permeation and selectivity in aquaporin water
channels.
Biophysical Journal, 85:2884-2899, 2003.
(PMC: 1303569)
JENS2003
Water permeation and electrostatic interactions between water
and channel are investigated in the E. coli glycerol uptake
facilitator GlpF, a member of the aquaporin water channel family,
by molecular dynamics simulations. A tetrameric model of the
channel embedded in a POPE membrane was used for the
simulations. During the simulations, water molecules pass
through the channel in single file.
The movement of the single file water molecules through the
channel is concerted, and we show that it can be described by a
continuous-time random-walk model. The integrity of the single
file remains intact during the permeation indicating that a disrupted
water chain is unlikely to be the mechanism of proton exclusion in
aquaporins. Specific hydrogen bonds between permeating water
and protein at the channel center (at two conserved Asp-Pro-Ala
(NPA) motifs), together with the protein electrostatic fields enforce
a bipolar water configuration inside the channel with dipole
inversion at the NPA motifs. At the NPA motifs water-protein
electrostatic interactions facilitate this inversion. Furthermore,
water-water electrostatic interactions are in all regions inside the
channel stronger than water-protein interactions, except near a
conserved, positively charged Arg residue. We find that variations
of the protein electrostatic field through the channel, owing to
preserved structural features, completely explain the bipolar
orientation of water. This orientation persists despite water
translocation in single file and blocks proton transport.
Furthermore, we find that also for permeation of a cation, ion-
protein electrostatic interactions are more unfavorable at the
conserved NPA motifs than at the conserved Arg, suggesting that
the major barrier against proton transport in aquaporins is faced at
the NPA motifs.
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