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PDBsum entry 5hxr
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Membrane protein
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PDB id
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5hxr
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References listed in PDB file
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Key reference
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Title
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Mechanism of extracellular ion exchange and binding-Site occlusion in a sodium/calcium exchanger.
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Authors
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J.Liao,
F.Marinelli,
C.Lee,
Y.Huang,
J.D.Faraldo-Gómez,
Y.Jiang.
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Ref.
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Nat Struct Biol, 2016,
23,
590-599.
[DOI no: ]
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PubMed id
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Abstract
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Na(+)/Ca(2+) exchangers use the Na(+) electrochemical gradient across the plasma
membrane to extrude intracellular Ca(2+) and play a central role in Ca(2+)
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(+), Ca(2+) or Sr(2+) 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(+)/Ca(2+)-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(+)/Ca(2+) antiport.
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Secondary reference #1
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Title
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Structural insight into the ion-Exchange mechanism of the sodium/calcium exchanger.
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Authors
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J.Liao,
H.Li,
W.Zeng,
D.B.Sauer,
R.Belmares,
Y.Jiang.
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Ref.
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Science, 2012,
335,
686-690.
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PubMed id
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