Three-dimensional organization of a human water channel

Abstract

Aquaporins (AQP) are members of the major intrinsic protein (MIP) superfamily of integral membrane proteins and facilitate water transport in various eukaryotes and prokaryotes1,2. The archetypal aquaporin AQP1 is a partly glycosylated water-selective channel3,4 that is widely expressed in the plasma membranes of several water-permeable epithelial and endothelial cells2,5. Here we report the three-dimensional structure of deglycosylated, human erythrocyte AQP1, determined at 7Å resolution in the membrane plane by electron crystallography of frozen-hydrated two-dimensional crystals6,7. The structure has an in-plane, intramolecular 2-fold axis of symmetry located in the hydrophobic core of the bilayer. The AQP1 monomer is composed of six membrane-spanning, tilted α-helices. These helices form a barrel that encloses a vestibular region leading to the water-selective channel, which is outlined by densities attributed to the functionally important NPA boxes8 and their bridges to the surrounding helices. The intramolecular symmetry within the AQP1 molecule represents a new motif for the topology and design of membrane protein channels, and is a simple and elegant solution to the problem of bidirectional transport across the bilayer.