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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


Human aquaporin 2 (AQP2) is a water channel found in the kidney collecting duct, where it plays a key role in concentrating urine. Water reabsorption is regulated by AQP2 trafficking between intracellular storage vesicles and the apical membrane. This process is tightly controlled by the pituitary hormone arginine vasopressin and defective trafficking results in nephrogenic diabetes insipidus (NDI). Here we present the X-ray structure of human AQP2 at 2.75 angstrom resolution. The C terminus of AQP2 displays multiple conformations with the C-terminal alpha-helix of one protomer interacting with the cytoplasmic surface of a symmetry-related AQP2 molecule, suggesting potential protein-protein interactions involved in cellular sorting of AQP2. Two Cd2+-ion binding sites are observed within the AQP2 tetramer, inducing a rearrangement of loop D, which facilitates this interaction. The locations of several NDI-causing mutations can be observed in the AQP2 structure, primarily situated within transmembrane domains and the majority of which cause misfolding and ER retention. These observations provide a framework for understanding why mutations in AQP2 cause NDI as well as structural insights into AQP2 interactions that may govern its trafficking.


  • Anna Frick
  • Urszula Kosinska Eriksson
  • Fabrizio de Mattia
  • Fredrik Oberg
  • Kristina Hedfalk
  • Richard Neutze
  • Willem J. de Grip
  • Peter M. T. Deen
  • Susanna Horsefield
Enheter & grupper

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Biologiska vetenskaper


Sidor (från-till)6305-6310
TidskriftProceedings of the National Academy of Sciences
StatusPublished - 2014
Peer review utfördJa