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.
journal_name
Proc Natl Acad Sci U S Aauthors
Levin EJ,Cao Y,Enkavi G,Quick M,Pan Y,Tajkhorshid E,Zhou Mdoi
10.1073/pnas.1207362109subject
Has Abstractpub_date
2012-07-10 00:00:00pages
11194-9issue
28eissn
0027-8424issn
1091-6490pii
1207362109journal_volume
109pub_type
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