title: Hydroxide and proton migration in aquaporins.
abstract: Hypothetical hydroxide and proton migration along the linear water chain in Aquaporin GlpF from Escherichia coli are studied by ab initio Car-Parrinello molecular dynamics simulations. It is found that the protein stabilizes a bipolar single file of water. The single file features a contiguous set of water-water hydrogen bonds in which polarization of the water molecules vary with position along the channel axis. Deprotonation of the water chain promotes the reorientation of water molecules while the hydroxide ion rapidly migrates by sequentially accepting protons from the neighboring water molecules. The hydroxide ion is not attracted by a conserved, channel-lining arginine residue, but is immobilized at two centrally located, conserved Asparagine-Proline-Alanine motifs where fourfold coordination stabilizes the ion. Hydroxide transition from the channel vestibules into the channel lumen is strongly influenced by electrostatic coupling to two conserved oppositely aligned macrodipoles. This suggests that the macrodipole's negative poles play a role in preventing hydroxide ions from entering into the channel's inner vestibules. Water protonation within the lumen facilitates water reorientation and subsequent proton expelling occurs. In the periplasmic half-channel, expelling occurs via the Grotthuss mechanism. Protonation within the cytoplasmic half-channel implies wire-breakage at the Asn-Pro-Ala motifs. The proton is here diffusively rejected as (H(5)O(2))(+).
authors.affiliation: MEMPHYS Center for Biomembrane Physics, Department of Physics, University of Southern Denmark, Odense, Denmark.
authors.forename: Morten Ø
authors.initials: MØ
authors.lastname: Jensen
authors.forename: Ursula
authors.initials: U
authors.lastname: Röthlisberger
authors.forename: Carme
authors.initials: C
authors.lastname: Rovira
mesh_terms: D000409:Alanine / Q000737:chemistry; D020816:Amino Acid Motifs; D020346:Aquaporins / Q000737:chemistry*; D001216:Asparagine / Q000737:chemistry; D001692:Biological Transport; D001703:Biophysics / Q000379:methods*; D003593:Cytoplasm / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D006860:Hydrogen Bonding; D006878:Hydroxides / Q000737:chemistry; D007477:Ions; D008051:Lipid Bilayers / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry; D019897:Periplasm / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry; D011392:Proline / Q000737:chemistry; D011522:Protons; D055672:Static Electricity; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D020346:Aquaporins; D029968:Escherichia coli Proteins; D006878:Hydroxides; D007477:Ions; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D011522:Protons; D014867:Water; C078043:GlpF protein, E coli; D001216:Asparagine; D006859:Hydrogen; C031356:hydroxide ion; D011392:Proline; D000409:Alanine; D010100:Oxygen; C028694:1-palmitoyl-2-oleoylphosphatidylcholine