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 (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 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 NCX_Mj and its ability to catalyze bidirectional ion-exchange reactions, we propose a structure model for the inward-facing NCX_Mj.
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040, USA.
Jun
J
Liao
Hua
H
Li
Weizhong
W
Zeng
David B
DB
Sauer
Ricardo
R
Belmares
Youxing
Y
Jiang
D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D003460:Crystallization; D018360:Crystallography, X-Ray; D017136:Ion Transport; D008024:Ligands; D017015:Methanococcales / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000737:chemistry* / Q000378:metabolism*
D019843:Archaeal Proteins; D008024:Ligands; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium