High-resolution x-ray structure of human aquaporin 5

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 36; pp. 13327 - 13332
• Main Authors: Horsefield, Rob, Nordén, Kristina, Fellert, Maria, Backmark, Anna, Törnroth-Horsefield, Susanna, Terwisscha van Scheltinga, Anke C, Kvassman, Jan, Kjellbom, Per, Johanson, Urban, Neutze, Richard
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 09.09.2008; National Acad Sciences
• Subjects: Aquaporin 5 - chemistry; Aquaporins; Biochemistry; Biologi; Biological Sciences; Cell membranes; Crystallization; crystallography; Crystallography, X-Ray; Electron density; Eukaryotes; heterologous overexpression; Humans; ions; Lipids; Lipids - chemistry; membrane protein; Membranes; Models, Molecular; Molecules; Natural Sciences; Naturvetenskap; Phosphorylation; physiological transport; Plasma; plasma membrane; Protein Structure, Quaternary; Protein Structure, Tertiary; Protein subunits; Proteins; Structural Homology, Protein; trafficking; water channel protein; Water channels; X-radiation; X-rays
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0801466105

Human aquaporin 5 (HsAQP5) facilitates the transport of water across plasma membranes and has been identified within cells of the stomach, duodenum, pancreas, airways, lungs, salivary glands, sweat glands, eyes, lacrimal glands, and the inner ear. AQP5, like AQP2, is subject to posttranslational regulation by phosphorylation, at which point it is trafficked between intracellular storage compartments and the plasma membrane. Details concerning the molecular mechanism of membrane trafficking are unknown. Here we report the x-ray structure of HsAQP5 to 2.0-Å resolution and highlight structural similarities and differences relative to other eukaryotic aquaporins. A lipid occludes the putative central pore, preventing the passage of gas or ions through the center of the tetramer. Multiple consensus phosphorylation sites are observed in the structure and their potential regulatory role is discussed. We postulate that a change in the conformation of the C terminus may arise from the phosphorylation of AQP5 and thereby signal trafficking.