title: 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 prokaryotes. The archetypal aquaporin AQP1 is a partly glycosylated water-selective channel that is widely expressed in the plasma membranes of several water-permeable epithelial and endothelial cells. Here we report the three-dimensional structure of deglycosylated, human erythrocyte AQP1, determined at 7 A resolution in the membrane plane by electron crystallography of frozen-hydrated two-dimensional crystals. The structure has an inplane, intramolecular 2-fold axis of symmetry located in the hydrophobic core of the bilayer. The AQP1 monomer is composed of six membrane-spanning, tilted alpha-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 boxes 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.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: A
authors.initials: A
authors.lastname: Cheng
authors.forename: A N
authors.initials: AN
authors.lastname: van Hoek
authors.forename: M
authors.initials: M
authors.lastname: Yeager
authors.forename: A S
authors.initials: AS
authors.lastname: Verkman
authors.forename: A K
authors.initials: AK
authors.lastname: Mitra
mesh_terms: D051398:Aquaporin 1; D020346:Aquaporins; D001789:Blood Group Antigens; D003460:Crystallization; D005615:Freezing; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007473:Ion Channels / Q000737:chemistry* / Q000648:ultrastructure; D008958:Models, Molecular; D011487:Protein Conformation; D014867:Water
chemical_list: C496020:AQP1 protein, human; D020346:Aquaporins; D001789:Blood Group Antigens; D007473:Ion Channels; D014867:Water; D051398:Aquaporin 1