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Structure of the sodium/iodide symporter (NIS) in complex with perrhenate and sodium
Structural highlights
FunctionSC5A5_RAT Sodium:iodide symporter that mediates the transport of iodide into the thyroid gland (PubMed:32084174, PubMed:8559252, PubMed:9341168). Can also mediate the transport of chlorate, thiocynate, nitrate and selenocynate (PubMed:9341168).[1] [2] [3] Publication Abstract from PubMedThe sodium/iodide symporter (NIS) is the essential plasma membrane protein that mediates active iodide (I(-)) transport into the thyroid gland, the first step in the biosynthesis of the thyroid hormones-the master regulators of intermediary metabolism. NIS couples the inward translocation of I(-) against its electrochemical gradient to the inward transport of Na(+) down its electrochemical gradient(1,2). For nearly 50 years before its molecular identification(3), NIS was the molecule at the centre of the single most effective internal radiation cancer therapy: radioiodide ((131)I(-)) treatment for thyroid cancer(2). Mutations in NIS cause congenital hypothyroidism, which must be treated immediately after birth to prevent stunted growth and cognitive deficiency(2). Here we report three structures of rat NIS, determined by single-particle cryo-electron microscopy: one with no substrates bound; one with two Na(+) and one I(-) bound; and one with one Na(+) and the oxyanion perrhenate bound. Structural analyses, functional characterization and computational studies show the substrate-binding sites and key residues for transport activity. Our results yield insights into how NIS selects, couples and translocates anions-thereby establishing a framework for understanding NIS function-and how it transports different substrates with different stoichiometries and releases substrates from its substrate-binding cavity into the cytosol. Structural insights into the mechanism of the sodium/iodide symporter.,Ravera S, Nicola JP, Salazar-De Simone G, Sigworth FJ, Karakas E, Amzel LM, Bianchet MA, Carrasco N Nature. 2022 Dec;612(7941):795-801. doi: 10.1038/s41586-022-05530-2. Epub 2022 , Dec 14. PMID:36517601[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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