Structural determinants of water permeation through aquaporin-1

Human red cell AQP1 is the first functionally defined member of the aquapor in family of membrane water channels. Here we describe an atomic model of A QP1 at 3.8 Angstrom resolution from electron crystallographic data. Multipl e highly conserved amino-acid residues stabilize the novel fold of AQP1. Th e aqueous pathway is lined with conserved hydrophobic residues that permit rapid water transport, whereas the water selectivity is due to a constricti on of the pore diameter to about 3 Angstrom over a span of one residue. The atomic model provides a possible molecular explanation to a longstanding p uzzle in physiology-how membranes can be freely permeable to water but impe rmeable to protons.