title: The 4.5 A structure of human AQP2.
abstract: Located in the principal cells of the collecting duct, aquaporin-2 (AQP2) is responsible for the regulated water reabsorption in the kidney and is indispensable for the maintenance of body water balance. Disregulation or malfunctioning of AQP2 can lead to severe diseases such as nephrogenic diabetes insipidus, congestive heart failure, liver cirrhosis and pre-eclampsia. Here we present the crystallization of recombinantly expressed human AQP2 into two-dimensional protein-lipid arrays and their structural characterization by atomic force microscopy and electron crystallography. These crystals are double-layered sheets that have a diameter of up to 30 microm, diffract to 3 A(-1) and are stacked by contacts between their cytosolic surfaces. The structure determined to 4.5 A resolution in the plane of the membrane reveals the typical aquaporin fold but also a particular structure between the stacked layers that is likely to be related to the cytosolic N and C termini.
authors.affiliation: M. E. Müller Institute for Microscopy, Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland. andreas.engel@unibas.ch
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Schenk
authors.forename: Paul J L
authors.initials: PJ
authors.lastname: Werten
authors.forename: Simon
authors.initials: S
authors.lastname: Scheuring
authors.forename: Bert L
authors.initials: BL
authors.lastname: de Groot
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Müller
authors.forename: Henning
authors.initials: H
authors.lastname: Stahlberg
authors.forename: Ansgar
authors.initials: A
authors.lastname: Philippsen
authors.forename: Andreas
authors.initials: A
authors.lastname: Engel
mesh_terms: D051399:Aquaporin 2; D020346:Aquaporins / Q000737:chemistry* / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D003460:Crystallization; D006801:Humans; D018625:Microscopy, Atomic Force; D017348:Microscopy, Electron, Scanning Transmission; D046529:Microscopy, Electron, Transmission
chemical_list: C496023:AQP2 protein, human; D051399:Aquaporin 2; D020346:Aquaporins