Crystallization and preliminary crystallographic analysis of human aquaporin 1 at a resolution of 3.28 Å

Abstract

Aquaporin water channels (AQPs) are found in almost every organism from humans to bacteria. In humans, 13 classes of AQPs control water and glycerol homeostasis. Knockout studies have suggested that modulating the activity of AQPs could be beneficial for the treatment of several pathologies. In particular, aquaporin 1 is a key factor in cell migration and angiogenesis, and constitutes a possible target for anticancer compounds and also for the treatment of glaucoma. Here, a preliminary crystallographic analysis at 3.28 Å resolution of crystals of human aquaporin 1 (hAQP1) obtained from protein expressed in Sf9 insect cells is reported. The crystals belonged to the tetragonal space groupI422, with unit-cell parametersa=b= 89.28,c= 174.9 Å, and contained one monomer per asymmetric unit. The hAQP1 biological tetramer is generatedviathe crystallographic fourfold axis. This work extends previous electron crystallographic studies that used material extracted from human red blood cells, in which the resolution was limited to approximately 3.8 Å. It will inform efforts to improve lattice contacts and the diffraction limit for the future structure-based discovery of specific hAQP1 inhibitors.