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XB-ART-57504
Nat Struct Mol Biol January 1, 2020; 27 (6): 533-539.
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Allosteric regulation of mammalian Na+/I- symporter activity by perchlorate.

Llorente-Esteban A , Manville RW , Reyna-Neyra A , Abbott GW , Amzel LM , Carrasco N .


Abstract
The Na+/I- symporter (NIS), the plasma membrane protein that actively transports I- (stoichiometry 2Na+:1I-) in thyroid physiology and radioiodide-based thyroid cancer treatment, also transports the environmental pollutant perchlorate (stoichiometry 1Na+:1ClO4-), which competes with I- for transport. Until now, the mechanism by which NIS transports different anion substrates with different stoichiometries has remained unelucidated. We carried out transport measurements and analyzed these using a statistical thermodynamics-based equation and electrophysiological experiments to show that the different stoichiometry of ClO4- transport is due to ClO4- binding to a high-affinity non-transport allosteric site that prevents Na+ from binding to one of its two sites. Furthermore, low concentrations of ClO4- inhibit I- transport not only by competition but also, critically, by changing the stoichiometry of I- transport to 1:1, which greatly reduces the driving force. The data reveal that ClO4- pollution in drinking water is more dangerous than previously thought.

PubMed ID: 32451489
Article link: Nat Struct Mol Biol
Grant support: [+]

Genes referenced: slc5a5
GO keywords: sodium ion transmembrane transport [+]

Disease Ontology terms: thyroid gland cancer