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Science 335 (6069): 686-690

Copyright © 2012 by the American Association for the Advancement of Science

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

Jun Liao,1,* Hua Li,1,2,* Weizhong Zeng,1,2 David B. Sauer,1 Ricardo Belmares,1,{dagger} Youxing Jiang1,2,{ddagger}

Abstract: Sodium/calcium (Na+/Ca2+) exchangers (NCX) are membrane transporters that play an essential role in maintaining the homeostasis of cytosolic Ca2+ for cell signaling. We demonstrated the Na+/Ca2+-exchange function of an NCX from Methanococcus jannaschii (NCX_Mj) and report its 1.9 angstrom crystal structure in an outward-facing conformation. Containing 10 transmembrane helices, the two halves of NCX_Mj share a similar structure with opposite orientation. Four ion-binding sites cluster at the center of the protein: one specific for Ca2+ and three that likely bind Na+. Two passageways allow for Na+ and Ca2+ access to the central ion-binding sites from the extracellular side. Based on the symmetry of NCX_Mj and its ability to catalyze bidirectional ion-exchange reactions, we propose a structure model for the inward-facing NCX_Mj.

1 Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390–9040, USA.
2 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390–9040, USA.

* These authors contributed equally to this work.

{dagger} Present address: North Crowley High School, Fort Worth, TX 76123, USA.

{ddagger} To whom correspondence should be addressed. E-mail: youxing.jiang{at}utsouthwestern.edu

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