5hxr

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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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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.
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Na+/Ca2+ exchangers use the Na+ electrochemical gradient across the plasma membrane to extrude intracellular Ca2+ and play a central role in Ca2+ homeostasis. Here, we elucidate their mechanisms of extracellular ion recognition and exchange through a structural analysis of the exchanger from Methanococcus jannaschii (NCX_Mj) bound to Na+, Ca2+ or Sr2+ in various occupancies and in an apo state. This analysis defines the binding mode and relative affinity of these ions, establishes the structural basis for the anticipated 3:1 Na+/Ca2+-exchange stoichiometry and reveals the conformational changes at the onset of the alternating-access transport mechanism. An independent analysis of the dynamics and conformational free-energy landscape of NCX_Mj in different ion-occupancy states, based on enhanced-sampling molecular dynamics simulations, demonstrates that the crystal structures reflect mechanistically relevant, interconverting conformations. These calculations also reveal the mechanism by which the outward-to-inward transition is controlled by the ion occupancy, thereby explaining the emergence of strictly coupled Na+/Ca2+ antiport.
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Structural insight into the ion-exchange mechanism of the sodium/calcium exchanger.,Liao J, Li H, Zeng W, Sauer DB, Belmares R, Jiang Y Science. 2012 Feb 10;335(6069):686-90. PMID:22323814<ref>PMID:22323814</ref>
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Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger.,Liao J, Marinelli F, Lee C, Huang Y, Faraldo-Gomez JD, Jiang Y Nat Struct Mol Biol. 2016 May 16. doi: 10.1038/nsmb.3230. PMID:27183196<ref>PMID:27183196</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

Revision as of 15:50, 23 June 2016

Structural mechanisms of extracellular ion exchange and induced binding-site occlusion in the sodium-calcium exchanger NCX_Mj soaked with 2.5 mM Na+ and 10mM Ca2+

5hxr, resolution 2.46Å

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