Structure-function relationships in aquaporins.
The identification of members of the aquaporin family as the primary water channels of cell membranes has been followed up by an intense effort to determine how these channels work. Specifically, investigators have sought to learn why these channels are selective for water and how they exclude proton trafficking. Molecular-dynamics studies using elegant, extremely detailed computer models based on accurate crystallographic maps of the channels show the basis for the selectivity of the channel. Channel size, the location of hydrophobic amino-acid side chains, and specific interactions of water dipoles with a charged residue near the most constricted point of the channel indicate that water molecules travel in single file through the center of the channel, and that the orientation of water molecules is manipulated to prevent the formation of a water wire spanning the channel. Finally, the number of water molecules calculated to be aligned in single file in the channel constriction fits predictions based on classic studies of the osmotic permeability: diffusive permeability ratios in water-permeable membranes.