Structure and permeation mechanism of a mammalian urea transporter

Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11194-9. doi: 10.1073/pnas.1207362109. Epub 2012 Jun 25.


As an adaptation to infrequent access to water, terrestrial mammals produce urine that is hyperosmotic to plasma. To prevent osmotic diuresis by the large quantity of urea generated by protein catabolism, the kidney epithelia contain facilitative urea transporters (UTs) that allow rapid equilibration between the urinary space and the hyperosmotic interstitium. Here we report the first X-ray crystal structure of a mammalian UT, UT-B, at a resolution of 2.36 Å. UT-B is a homotrimer and each protomer contains a urea conduction pore with a narrow selectivity filter. Structural analyses and molecular dynamics simulations showed that the selectivity filter has two urea binding sites separated by an approximately 5.0 kcal/mol energy barrier. Functional studies showed that the rate of urea conduction in UT-B is increased by hypoosmotic stress, and that the site of osmoregulation coincides with the location of the energy barrier.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Cloning, Molecular
  • Crystallography, X-Ray / methods
  • Humans
  • Kidney / metabolism*
  • Ligands
  • Liposomes / chemistry
  • Membrane Transport Proteins / chemistry*
  • Metabolism
  • Models, Molecular
  • Molecular Conformation
  • Molecular Dynamics Simulation
  • Osmosis
  • Proteins / chemistry
  • Urea / chemistry
  • Xenopus laevis


  • Ligands
  • Liposomes
  • Membrane Transport Proteins
  • Proteins
  • urea transporter
  • Urea

Associated data

  • PDB/4EZC
  • PDB/4EZD