Structural highlights
Function
[UT1_BOVIN] Urea channel that facilitates transmembrane urea transport down a concentration gradient. A constriction of the transmembrane channel functions as selectivity filter through which urea is expected to pass in dehydrated form. The rate of urea conduction is increased by hypotonic stress. Plays an important role in the kidney medulla collecting ducts, where it allows rapid equilibration between the lumen of the collecting ducts and the interstitium, and thereby prevents water loss driven by the high concentration of urea in the urine. Facilitates urea transport across erythrocyte membranes. May also play a role in transmembrane water transport, possibly by indirect means.[1] [2]
Publication Abstract from PubMed
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 A. 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.
Structure and permeation mechanism of a mammalian urea transporter.,Levin EJ, Cao Y, Enkavi G, Quick M, Pan Y, Tajkhorshid E, Zhou M Proc Natl Acad Sci U S A. 2012 Jun 25. PMID:22733730[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Stewart GS, Graham C, Cattell S, Smith TP, Simmons NL, Smith CP. UT-B is expressed in bovine rumen: potential role in ruminal urea transport. Am J Physiol Regul Integr Comp Physiol. 2005 Aug;289(2):R605-R612. Epub, 2005 Apr 21. PMID:15845882 doi:http://dx.doi.org/00127.2005
- ↑ Levin EJ, Cao Y, Enkavi G, Quick M, Pan Y, Tajkhorshid E, Zhou M. Structure and permeation mechanism of a mammalian urea transporter. Proc Natl Acad Sci U S A. 2012 Jun 25. PMID:22733730 doi:10.1073/pnas.1207362109
- ↑ Levin EJ, Cao Y, Enkavi G, Quick M, Pan Y, Tajkhorshid E, Zhou M. Structure and permeation mechanism of a mammalian urea transporter. Proc Natl Acad Sci U S A. 2012 Jun 25. PMID:22733730 doi:10.1073/pnas.1207362109
