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

Sodium/calcium (Na (+) /Ca (2+) ) exchangers (NCX) are membrane transporters that play an essential role in maintaining the homeostasis of cytosolic Ca (2+) for cell signaling. We demonstrated the Na (+) /Ca (2+) -exchange function of an NCX from Methanococcus jannaschii (NCXMj) and report its 1. 9 angstrom crystal structure in an outward-facing conformation. Containing 10 transmembrane helices, the two halves of NCXMj share a similar structure with opposite orientation. Four ion-binding sites cluster at the center of the protein: one specific for Ca (2+) and three that likely bind Na (+). Two passageways allow for Na (+) and Ca (2+) access to the central ion-binding sites from the extracellular side. Based on the symmetry of NCXMj and its ability to catalyze bidirectional ion-exchange reactions, we propose a structure model for the inward-facing NCXMj.