5JDH

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.196 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger.

Liao, J.Marinelli, F.Lee, C.Huang, Y.Faraldo-Gomez, J.D.Jiang, Y.

(2016) Nat Struct Mol Biol 23: 590-599

  • DOI: https://doi.org/10.1038/nsmb.3230
  • Primary Citation of Related Structures:  
    5HWX, 5HWY, 5HXC, 5HXE, 5HXH, 5HXR, 5HXS, 5HYA, 5JDF, 5JDG, 5JDH, 5JDL, 5JDM, 5JDN, 5JDQ

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    School of Life Science and Technology, ShanghaiTech University, Shanghai, P.R. China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Uncharacterized membrane protein MJ0091301Methanocaldococcus jannaschii DSM 2661Mutation(s): 1 
Gene Names: MJ0091
Membrane Entity: Yes 
UniProt
Find proteins for Q57556 (Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440))
Explore Q57556 
Go to UniProtKB:  Q57556
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ57556
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 8 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PE8
Query on PE8

Download Ideal Coordinates CCD File 
T [auth A]3,6,9,12,15,18,21-HEPTAOXATRICOSANE-1,23-DIOL
C16 H34 O9
GLZWNFNQMJAZGY-UHFFFAOYSA-N
OLC
Query on OLC

Download Ideal Coordinates CCD File 
W [auth A](2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate
C21 H40 O4
RZRNAYUHWVFMIP-GDCKJWNLSA-N
1PE
Query on 1PE

Download Ideal Coordinates CCD File 
R [auth A],
S [auth A],
U [auth A]
PENTAETHYLENE GLYCOL
C10 H22 O6
JLFNLZLINWHATN-UHFFFAOYSA-N
MYS
Query on MYS

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F [auth A]
G [auth A]
H [auth A]
I [auth A]
J [auth A]
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
N [auth A],
O [auth A],
P [auth A],
Q [auth A]
PENTADECANE
C15 H32
YCOZIPAWZNQLMR-UHFFFAOYSA-N
PEG
Query on PEG

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V [auth A]DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
CA
Query on CA

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D [auth A],
E [auth A]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
CL
Query on CL

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B [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
NA
Query on NA

Download Ideal Coordinates CCD File 
C [auth A]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.196 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.883α = 90
b = 72.218β = 90
c = 96.099γ = 90
Software Package:
Software NamePurpose
HKL-2000data scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Howard Hughes Medical Institute (HHMI)United Statesfunding for Youxing Jiang
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR01GM079179
Welch FoundationUnited StatesGrant I-1578
National Natural Science Foundation of China (NSFC)ChinaProject 31470817
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)United Statesfunding for Jose D. Faraldo-Gomez

Revision History  (Full details and data files)

  • Version 1.0: 2016-05-11
    Type: Initial release
  • Version 1.1: 2016-06-01
    Changes: Database references
  • Version 1.2: 2016-06-15
    Changes: Database references
  • Version 1.3: 2017-09-20
    Changes: Author supporting evidence, Derived calculations
  • Version 1.4: 2019-11-20
    Changes: Author supporting evidence
  • Version 1.5: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description