X-ray structure of human aquaporin 2 and its implications for nephrogenic diabetes insipidus and trafficking

摘要: Human aquaporin 2 (AQP2) is a water channel found in the kidney collecting duct, where it plays key role concentrating urine. Water reabsorption regulated by AQP2 trafficking between intracellular storage vesicles and apical membrane. This process tightly controlled pituitary hormone arginine vasopressin defective results nephrogenic diabetes insipidus (NDI). Here we present X-ray structure of human at 2.75 A resolution. The C terminus displays multiple conformations with C-terminal α-helix one protomer interacting cytoplasmic surface symmetry-related molecule, suggesting potential protein-protein interactions involved cellular sorting AQP2. Two Cd(2+)-ion binding sites are observed within tetramer, inducing rearrangement loop D, which facilitates this interaction. locations several NDI-causing mutations can be structure, primarily situated transmembrane domains majority cause misfolding ER retention. These observations provide framework for understanding why NDI as well structural insights into that may govern its trafficking.