Allosteric regulation of mammalian Na+/I− symporter activity by perchlorate

Alejandro Llorente-Esteban, Rian Manville, Andrea Reyna-Neyra, Geoffrey Abbott, L Mario Amzel, Nancy Carrasco

    Research output: Contribution to journalArticlepeer-review


    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 +:1ClO 4 ), 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 ClO 4 transport is due to ClO 4 binding to a high-affinity non-transport allosteric site that prevents Na + from binding to one of its two sites. Furthermore, low concentrations of ClO 4 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 ClO 4 pollution in drinking water is more dangerous than previously thought.

    Original languageEnglish
    Pages (from-to)533-539
    Number of pages7
    JournalNature Structural and Molecular Biology
    Issue number6
    Publication statusPublished - 25 May 2020


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