Structural Insight into the Ion-Exchange Mechanism of the Sodium/Calcium Exchanger

Maintaining Equilibrium Na + /Ca 2+ exchangers (NCX) are membrane transporters that maintain the homeostasis of cytosolic Ca 2+ and play an essential role in Ca 2+ signaling. Despite a long history of physiological work and a large body of functional data, the structural basis underlying the ion exchange mechanism of NCX is poorly understood. Liao et al. (p. 686 ; see the Perspective by Abramson et al. ) present a high-resolution crystal structure of an NCX from Methanococcus jannaschii and demonstrate that this archaeal NCX catalyzes Na + /Ca 2+ -exchange reactions similar to its eukaryotic counterpart. The structure clarifies the mechanism of ion exchange proteins and reveals the basis for the stoichiometry, cooperativity, and bidirectionality of the reaction.