Mechanism of anion selectivity and stoichiometry of the Na + /I - symporter (NIS)
Year: 2011
Type: article
Abstract: I(-) uptake in the thyroid, the first step in thyroid hormone biosynthesis, is mediated by the Na(+)/I(-) symporter (NIS) with an electrogenic 2Na(+):1I(-) stoichiometry. We have obtained mechanistic information on NIS by characterizing the congenital I(-) transport defect-causing NIS mutant G93R. This mutant is targeted to the plasma membrane but is inactive. Substitutions at position 93 show that the longer the side chain of the neutral residue at this position, the higher the K(m) for the anion substrates. Unlike WT NIS, which mediates symport of Na(+) and the environmental pollutant perchlorate electroneutrally, G93T/N/Q/E/D NIS, strikingly, do it electrogenically with a 21 stoichiometry. Furthermore, G93E/Q NIS discriminate between anion substrates, a discovery with potential clinical relevance. A 3D homology model of NIS based on the structure of the bacterial Na(+)/galactose transporter identifies G93 as a critical player in the mechanism of the transporter: the changes from an outwardly to an inwardly open conformation during the transport cycle use G93 as a pivot.
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
Awards: Molecular Characterization of the Sodium/Iodide Symporter (NIS), Redox signaling in axon guidance: Structure and activity of MICAL, Integration of Biomedical Research into Education of Future PhD Candidates, G2676781635, G317510355, The mammary gland sodium/iodide symporter (mgNIS), Molecular Physiology of y-Aminobutyric Acid Transporters, G7271471622, G8595184336, Medical Scientist Training Program
OpenAlex ID: W2043682449