Switch from an aquaporin to a glycerol channel by two amino acids substitution

The MIP (major intrinsic protein) proteins constitute a channel family of c urrently 150 members that have been identified in cell membranes of organis ms ranging from bacteria to man. Among these proteins, two functionally dis tinct subgroups are characterized: aquaporins that allow specific water tra nsfer and glycerol channels that are involved in glycerol and small neutral solutes transport. Since the flow of small molecules across cell membranes is vital for every living organism, the study of such proteins is of parti cular interest, For instance, aquaporins located in kidney cell membranes a re responsible for reabsorption of 150 liters of water/ day in adult human. To understand the molecular mechanisms of solute transport specificity, we analyzed mutant aquaporins in which highly conserved residues have been su bstituted by amino acids located at the same positions in glycerol channels . Here, we show that substitution of a tyrosine and a tryptophan by a proli ne and a leucine, respectively, in the sixth transmembrane helix of an aqua porin leads to a switch in the selectivity of the channel, from water to gl ycerol.