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Structure and permeation mechanism of a mammalian urea transporter.

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 ?. 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.

SUBMITTER: Levin EJ

PROVIDER: S-EPMC3396522 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Structure and permeation mechanism of a mammalian urea transporter.

Levin Elena J EJ Cao Yu Y Enkavi Giray G Quick Matthias M Pan Yaping Y Tajkhorshid Emad E Zhou Ming M

Proceedings of the National Academy of Sciences of the United States of America 20120625 28

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 protom ...[more]

PMID: 22733730

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