ArticleProceedings of the National Academy of Sciences of the United States of America2012
Structure and permeation mechanism of a mammalian urea transporter.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 82 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Hotspot pocket-based discovery of urea transporter selective inhibitors.Nature communications · 2026Article
- The RNF/NQR redox pumps: a versatile system for energy transduction in bacteria and archaea.Applied microbiology and biotechnology · 2025Review
- Ammonia transport mediated by urea transporter A isoforms.Biology open · 2025Article
- Protein Structures of Urea Transporters.Sub-cellular biochemistry · 2025Review
- Transport Characteristics of Urea Transporters.Sub-cellular biochemistry · 2025Review
- Urea Transport Mediated by Membrane Proteins of Non-urea-Transporters.Sub-cellular biochemistry · 2025Review
- Structural insights into the mechanisms of urea permeation and distinct inhibition modes of urea transporters.Nature communications · 2024Article
- Conformational coupling of redox-driven NaNature structural & molecular biology · 2023Article
- Structural characterization of human urea transporters UT-A and UT-B and their inhibition.Science advances · 2023Article
- Urea and water are transported through different pathways in the red blood cell membrane.The Journal of general physiology · 2023Article
- Substrate Recognition Properties from an Intermediate Structural State of the UreA Transporter.International journal of molecular sciences · 2022Article
- A critical analysis of urea transporter B inhibitors: molecular fingerprints, pharmacophore features for the development of next-generation diuretics.Molecular diversity · 2022Article
- The role of rumen epithelial urea transport proteins in urea nitrogen salvage: A review.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2022Review
- VARIDT 2.0: structural variability of drug transporter.Nucleic acids research · 2022Article
- Urea transport and hydrolysis in the rumen: A review.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2021Review
- Water in Nanopores and Biological Channels: A Molecular Simulation Perspective.Chemical reviews · 2020Review
- Water transport mediated by murine urea transporters: implications for urine concentration mechanisms.Biology open · 2020Article
- Urea-aromatic interactions in biology.Biophysical reviews · 2020Review
- Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.Chemical reviews · 2019Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
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.
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