Evidence map›Paper›PMID 27183196›Full record

ArticleNature structural & molecular biology2016

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

Jun Liao, Fabrizio Marinelli, ChangKeun Lee, Yihe Huang, José D Faraldo-Gómez, Youxing Jiang

Open access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. The NaThe Journal of veterinary medical science · 2026
    Review
  5. Molecular mechanisms of mitochondrial CaNature communications · 2026
    Article
  6. Molecular mechanisms of mitochondrial CabioRxiv : the preprint server for biology · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Novel impact of metal ion-induced cell death on diabetic cardiomyopathy pathogenesis and therapy.Apoptosis : an international journal on programmed cell death · 2025
    Review
  13. Article
  14. Article
  15. Article
  16. International journal of molecular sciences · 2024
    Article
  17. Conformational free-energy landscapes of a NaProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  18. Structural dynamics of NaCommunications biology · 2024
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 2 countries.

Jun Liao *School of Life Science and Technology, ShanghaiTech University, Shanghai, P.R. China.
Fabrizio Marinelli *Theoretical Molecular Biophysics Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
ChangKeun LeeDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yihe HuangDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
José D Faraldo-GómezTheoretical Molecular Biophysics Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Youxing JiangDepartment of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
National Institutes of Health · USThe University of Texas Southwestern Medical Center · USShanghaiTech University · CNSouthwestern Medical Center · US

Funding

Molecular Mechanisms in Membrane Bioenergetics, Transport and SignalingZIAHL006203 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI FARALDO-GÓMEZ, JOSE · 2015 to 2023
$15.4M
Structural mechanisms of ion selectivity and gating in tetrameric cation channelsR01GM079179 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI JIANG, YOUXING · 2007 to 2019
$3.5M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM079179
6 · The paper itself

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.

Indexed as

Archaeal ProteinsBinding SitesCalciumCrystallography, X-RayIon ExchangeMethanocaldococcusMolecular Docking SimulationMolecular Dynamics SimulationProtein ConformationSodiumSodium-Calcium ExchangerStrontiumArchaeal ProteinsCalciumSodiumSodium-Calcium ExchangerStrontium

Identifiers

PMID27183196
PMCPMC4918766
OpenAlexW2405114694

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.