Abstract
"Real time" molecular dynamics simulations of water permeation through human aquaporin-1 (AQP1) and the bacterial glycerol facilitator GlpF are presented. We obtained time-resolved, atomic-resolution models of the permeation mechanism across these highly selective membrane channels. Both proteins act as two-stage filters: Conserved fingerprint [asparagine-proline-alanine (NPA)] motifs form a selectivity-determining region; a second (aromatic/arginine) region is proposed to function as a proton filter. Hydrophobic regions near the NPA motifs are rate-limiting water barriers. In AQP1, a fine-tuned water dipole rotation during passage is essential for water selectivity. In GlpF, a glycerol-mediated "induced fit" gating motion is proposed to generate selectivity for glycerol over water.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Aquaporin 1
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Aquaporins / chemistry*
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Aquaporins / metabolism*
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Bacterial Outer Membrane Proteins / chemistry*
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Bacterial Outer Membrane Proteins / metabolism*
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Cell Membrane Permeability
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Computer Simulation*
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Crystallography, X-Ray
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Escherichia coli Proteins*
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Glycerol / metabolism
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Hydrogen Bonding
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Hydrophobic and Hydrophilic Interactions
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Kinetics
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Lipid Bilayers
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Membrane Potentials
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Models, Biological
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Models, Molecular
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Permeability
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Protein Conformation
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Protein Structure, Secondary
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Protons
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Static Electricity
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Thermodynamics
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Time Factors
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Water / chemistry
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Water / metabolism*
Substances
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Aquaporins
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Bacterial Outer Membrane Proteins
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Escherichia coli Proteins
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Lipid Bilayers
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Protons
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Water
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GlpF protein, E coli
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Aquaporin 1
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Glycerol