Schematic architecture of the channel within an AQP1 subunit (sagittal section). The shape of the aqueous pore (blue) is derived from calculations based on the structure of bovine AQP1 (9). Four water molecules shown in bold colors represent transient interactions with the pore-lining residues at discrete sites. Bulk water in the extracellular and intracellular vestibules is depicted in pastels. Three features of the channel specify selectivity for water: (a) Size restriction. Eight angstroms above the midpoint of the channel, the pore narrows to a diameter of 2.8 Å (approximately the diameter of a water molecule). (b) Electrostatic repulsion. A conserved residue (Arg-195) at the narrowest constriction of the pore imposes a barrier to cations, including protonated water (H₃O⁺). (c) Water dipole reorientation. Two partial helices meet at the midpoint of the channel, providing positively charged dipoles that reorient a water molecule as it traverses this point. Disrupting hydrogen bonding in the single-file chain water molecules prevents the formation of a proton conductance. A video animation of water molecules passing through the AQP1 protein is available on the internet at http://www.mpibpc.gwdg.de/abteilungen/071/bgroot/presentations/aqp1_dyn/aqp1_mono.html.