Evidence map›Paper›PMID 24558365›Full record

ArticlePloS one2014

Molecular dynamics simulations of the cardiac troponin complex performed with FRET distances as restraints.

Jayant James Jayasundar, Jun Xing, John M Robinson, Herbert C Cheung, Wen-Ji Dong

Abstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
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

24 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. The missing links within troponin.Archives of biochemistry and biophysics · 2019
    Review
  10. Computational Studies of Cardiac and Skeletal Troponin.Frontiers in molecular biosciences · 2019
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
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

5 authors.

Jayant James JayasundarVoiland School of Chemical Engineering and Bioengineering and The Department of Integrated Physiology and Neuroscience, Washington State University, Pullman, Washington, United States of America.
Jun XingVoiland School of Chemical Engineering and Bioengineering and The Department of Integrated Physiology and Neuroscience, Washington State University, Pullman, Washington, United States of America.
John M RobinsonDepartment of Chemistry and Biochemistry, South Dakota State University, Brookings, South Dakota, United States of America.
Herbert C CheungThe Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Wen-Ji DongVoiland School of Chemical Engineering and Bioengineering and The Department of Integrated Physiology and Neuroscience, Washington State University, Pullman, Washington, United States of America.

Funding

Kinetics of Cardiac Myofilament ActivationR01HL080186 · NHLBI · WASHINGTON STATE UNIVERSITY · PI DONG, WEN-JI · 2005 to 2013
$3.4M
REGULATORY MECHANISMS OF CARDIAC MUSCLER01HL052508 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CHEUNG, HERBERT C · 1996 to 2008
$2.6M
NHLBI NIH HHS HL52508NHLBI NIH HHS HL80186NHLBI NIH HHS R01 HL052508NHLBI NIH HHS R01 HL080186
6 · The paper itself

Abstract

Cardiac troponin (cTn) is the Ca(2+)-sensitive molecular switch that controls cardiac muscle activation and relaxation. However, the molecular detail of the switching mechanism and how the Ca(2+) signal received at cardiac troponin C (cTnC) is communicated to cardiac troponin I (cTnI) are still elusive. To unravel the structural details of troponin switching, we performed ensemble Förster resonance energy transfer (FRET) measurements and molecular dynamic (MD) simulations of the cardiac troponin core domain complex. The distance distributions of forty five inter-residue pairs were obtained under Ca(2+)-free and saturating Ca(2+) conditions from time-resolved FRET measurements. These distances were incorporated as restraints during the MD simulations of the cardiac troponin core domain. Compared to the Ca(2+)-saturated structure, the absence of regulatory Ca(2+) perturbed the cTnC N-domain hydrophobic pocket which assumed a closed conformation. This event partially unfolded the cTnI regulatory region/switch. The absence of Ca(2+), induced flexibility to the D/E linker and the cTnI inhibitory region, and rotated the cTnC N-domain with respect to rest of the troponin core domain. In the presence of saturating Ca(2+) the above said phenomenon were absent. We postulate that the secondary structure perturbations experienced by the cTnI regulatory region held within the cTnC N-domain hydrophobic pocket, coupled with the rotation of the cTnC N-domain would control the cTnI mobile domain interaction with actin. Concomitantly the rotation of the cTnC N-domain and perturbation of the D/E linker rigidity would control the cTnI inhibitory region interaction with actin to effect muscle relaxation.

Indexed as

Molecular Dynamics SimulationActinsAnimalsCalciumFluorescence Resonance Energy TransferHydrogen BondingHydrophobic and Hydrophilic InteractionsLigandsMiceModels, StatisticalMyocardiumProtein BindingProtein Structure, SecondaryProtein Structure, TertiaryRatsRecombinant ProteinsActinsCalciumLigandsRecombinant ProteinsTroponin C

Identifiers

PMID24558365
PMCPMC3928104

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Registered trials

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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.