LAUSR

Structural Biology To make thyroid hormones, which are critical in development, iodine ions (I−) must be transported into thyroid cells. This is achieved by the sodium ion (Na+)/I− symporter (NIS), which couples the energetically unfavorable import of one I− with the energetically favorable import of two Na+. NIS also transports the environmental pollutant perchlorate (ClO4−), but in this case couples transport of one ClO4− with that of one Na+. Based on theory and experiments, Llorente-Esteban et al. show that ClO4− binds not only to the transport site but also to a nontransport site. Binding at the second site precludes binding of one of the Na+. Therefore, ClO4− not only inhibits I− transport by direct competition, it also reduces the driving force for I− transport by binding at the nontransport site. Nat. Struct. Mol. Biol. 27 , 533 (2020).