Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2012 Jul 10;10928:11194-9. doi: 10.1073/pnas.1207362109.
Show Gene links
Show Anatomy links
Structure and permeation mechanism of a mammalian urea transporter.
Levin EJ
,
Cao Y
,
Enkavi G
,
Quick M
,
Pan Y
,
Tajkhorshid E
,
Zhou M
.
???displayArticle.abstract???
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.
Adams,
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
2010, Pubmed
Adams,
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
2010,
Pubmed
Bankir,
New insights into urea and glucose handling by the kidney, and the urine concentrating mechanism.
2012,
Pubmed
Bankir,
Direct and indirect cost of urea excretion.
1996,
Pubmed
Beitz,
Point mutations in the aromatic/arginine region in aquaporin 1 allow passage of urea, glycerol, ammonia, and protons.
2006,
Pubmed
,
Xenbase
Blount,
Forskolin stimulates phosphorylation and membrane accumulation of UT-A3.
2007,
Pubmed
Caflisch,
Structural details of urea binding to barnase: a molecular dynamics analysis.
1999,
Pubmed
Chen,
MolProbity: all-atom structure validation for macromolecular crystallography.
2010,
Pubmed
de Groot,
Water permeation across biological membranes: mechanism and dynamics of aquaporin-1 and GlpF.
2001,
Pubmed
Dodson,
Collaborative Computational Project, number 4: providing programs for protein crystallography.
1997,
Pubmed
Doran,
Tissue distribution of UT-A and UT-B mRNA and protein in rat.
2006,
Pubmed
Emsley,
Coot: model-building tools for molecular graphics.
2004,
Pubmed
Fenton,
Renal phenotype of UT-A urea transporter knockout mice.
2005,
Pubmed
Fenton,
Urinary concentrating defect in mice with selective deletion of phloretin-sensitive urea transporters in the renal collecting duct.
2004,
Pubmed
Garcia-Closas,
A genome-wide association study of bladder cancer identifies a new susceptibility locus within SLC14A1, a urea transporter gene on chromosome 18q12.3.
2011,
Pubmed
Hediger,
Structure, regulation and physiological roles of urea transporters.
1996,
Pubmed
,
Xenbase
Hoffert,
Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites.
2006,
Pubmed
Hub,
Mechanism of selectivity in aquaporins and aquaglyceroporins.
2008,
Pubmed
Humphrey,
VMD: visual molecular dynamics.
1996,
Pubmed
Khademi,
Mechanism of ammonia transport by Amt/MEP/Rh: structure of AmtB at 1.35 A.
2004,
Pubmed
Klauda,
Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types.
2010,
Pubmed
Klein,
Vasopressin increases plasma membrane accumulation of urea transporter UT-A1 in rat inner medullary collecting ducts.
2006,
Pubmed
Klein,
Urea transport in the kidney.
2011,
Pubmed
Kokko,
Countercurrent multiplication system without active transport in inner medulla.
1972,
Pubmed
Layton,
Role of UTB urea transporters in the urine concentrating mechanism of the rat kidney.
2007,
Pubmed
Lei,
Role of thin descending limb urea transport in renal urea handling and the urine concentrating mechanism.
2011,
Pubmed
Levin,
Crystal structure of a bacterial homologue of the kidney urea transporter.
2009,
Pubmed
,
Xenbase
Maciver,
Functional characterization of mouse urea transporters UT-A2 and UT-A3 expressed in purified Xenopus laevis oocyte plasma membranes.
2008,
Pubmed
,
Xenbase
Mackerell,
Extending the treatment of backbone energetics in protein force fields: limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations.
2004,
Pubmed
Mannuzzu,
Estimate of the number of urea transport sites in erythrocyte ghosts using a hydrophobic mercurial.
1993,
Pubmed
Mathai,
Measurement of water and solute permeability by stopped-flow fluorimetry.
2007,
Pubmed
McCoy,
Phaser crystallographic software.
2007,
Pubmed
Minocha,
The urea transporter (UT) family: bioinformatic analyses leading to structural, functional, and evolutionary predictions.
2003,
Pubmed
Newby,
Crystal structure of the aquaglyceroporin PfAQP from the malarial parasite Plasmodium falciparum.
2008,
Pubmed
Northrup,
Dynamical theory of activated processes in globular proteins.
1982,
Pubmed
Painter,
Optimal description of a protein structure in terms of multiple groups undergoing TLS motion.
2006,
Pubmed
Pallone,
Evidence that aquaporin-1 mediates NaCl-induced water flux across descending vasa recta.
1997,
Pubmed
Rafnar,
European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.
2011,
Pubmed
Ranade,
Genetic variation in the human urea transporter-2 is associated with variation in blood pressure.
2001,
Pubmed
Raunser,
Oligomeric structure and functional characterization of the urea transporter from Actinobacillus pleuropneumoniae.
2009,
Pubmed
Rousselet,
Tandem sequence repeats in urea transporters: identification of an urea transporter signature sequence.
1996,
Pubmed
Sands,
Mammalian urea transporters.
2003,
Pubmed
Stephenson,
Concentration of urine in a central core model of the renal counterflow system.
1972,
Pubmed
Stewart,
Vasopressin regulation of the renal UT-A3 urea transporter.
2009,
Pubmed
Sui,
Structural basis of water-specific transport through the AQP1 water channel.
,
Pubmed
Tajkhorshid,
Control of the selectivity of the aquaporin water channel family by global orientational tuning.
2002,
Pubmed
Uchida,
Impaired urea accumulation in the inner medulla of mice lacking the urea transporter UT-A2.
2005,
Pubmed
Wang,
What makes an aquaporin a glycerol channel? A comparative study of AqpZ and GlpF.
2005,
Pubmed
Yang,
Urea transporter UT3 functions as an efficient water channel. Direct evidence for a common water/urea pathway.
1998,
Pubmed
,
Xenbase
Yang,
Analysis of double knockout mice lacking aquaporin-1 and urea transporter UT-B. Evidence for UT-B-facilitated water transport in erythrocytes.
2002,
Pubmed
,
Xenbase
Yang,
Urea-selective concentrating defect in transgenic mice lacking urea transporter UT-B.
2002,
Pubmed
Zhang,
Vasopressin rapidly increases phosphorylation of UT-A1 urea transporter in rat IMCDs through PKA.
2002,
Pubmed
Zhao,
Comparative transport efficiencies of urea analogues through urea transporter UT-B.
2007,
Pubmed
Zheng,
The mechanism of ammonia transport based on the crystal structure of AmtB of Escherichia coli.
2004,
Pubmed
