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The 4.5Å Structure of Human AQP2

2005; Elsevier BV; Volume: 350; Issue: 2 Linguagem: Inglês

10.1016/j.jmb.2005.04.030

1089-8638

Andreas D. Schenk, Paul J.L. Werten, Simon Scheuring, Bert L. de Groot, Shirley A. Müller, Henning Stahlberg, Ansgar Philippsen, Andreas Engel,

Ion channel regulation and function

Located in the principal cells of the collecting duct, aquaporin-2 (AQP2) is responsible for the regulated water reabsorbtion 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 μm, diffract to 3 Å−1 and are stacked by contacts between their cytosolic surfaces. The structure determined to 4.5 Å 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.