Crystal structure of a bacterial homologue of the kidney urea transporter

Nature. 2009 Dec 10;462(7274):757-61. doi: 10.1038/nature08558.

Abstract

Urea is highly concentrated in the mammalian kidney to produce the osmotic gradient necessary for water re-absorption. Free diffusion of urea across cell membranes is slow owing to its high polarity, and specialized urea transporters have evolved to achieve rapid and selective urea permeation. Here we present the 2.3 A structure of a functional urea transporter from the bacterium Desulfovibrio vulgaris. The transporter is a homotrimer, and each subunit contains a continuous membrane-spanning pore formed by the two homologous halves of the protein. The pore contains a constricted selectivity filter that can accommodate several dehydrated urea molecules in single file. Backbone and side-chain oxygen atoms provide continuous coordination of urea as it progresses through the filter, and well-placed alpha-helix dipoles provide further compensation for dehydration energy. These results establish that the urea transporter operates by a channel-like mechanism and reveal the physical and chemical basis of urea selectivity.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Desulfovibrio vulgaris / chemistry*
  • Humans
  • Kidney / chemistry*
  • Membrane Transport Proteins / chemistry*
  • Membrane Transport Proteins / metabolism*
  • Models, Molecular
  • Oocytes / metabolism
  • Protein Folding
  • Protein Structure, Quaternary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Structure-Activity Relationship
  • Urea / metabolism
  • Urea Transporters
  • Xenopus laevis

Substances

  • Membrane Transport Proteins
  • Protein Subunits
  • Urea

Associated data

  • PDB/3K3F
  • PDB/3K3G