Evidence map›Paper›PMID 15531631›Full record

ArticleBiophysical journal2005

Mechanically induced titin kinase activation studied by force-probe molecular dynamics simulations.

Frauke Gräter, Jianhua Shen, Hualiang Jiang, Mathias Gautel, Helmut Grubmüller

Open access · bronzeAbstract readEvaluation StudyValidation Study
In one paragraph

Article in Biophysical journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
8.0field-weighted citation impact, top 2% 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

89 citing papers in PubMed, 220 citations in OpenAlex.

  1. Single-Molecule Force Spectroscopy: Experiments, Analysis, and Simulations.Methods in molecular biology (Clifton, N.J.) · 2027
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Contribution of hydrophobic interactions to protein mechanical stability.Computational and structural biotechnology journal · 2022
    Article
  20. Article

29 more citing papers are in PubMed but not listed here.

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 at 3 institutions in 3 countries.

Frauke GräterTheoretical and Computational Biophysics Department, Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Jianhua Shen
Hualiang Jiang
Mathias Gautel
Helmut Grubmüller
Max Planck Institute for Biophysical Chemistry · DEShanghai Institute of Materia Medica · CNKing's College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The conversion of mechanical stress into a biochemical signal in a muscle cell requires a force sensor. Titin kinase, the catalytic domain of the elastic muscle protein titin, has been suggested as a candidate. Its activation requires major conformational changes resulting in the exposure of its active site. Here, force-probe molecular dynamics simulations were used to obtain insight into the tension-induced activation mechanism. We find evidence for a sequential mechanically induced opening of the catalytic site without complete domain unfolding. Our results suggest the rupture of two terminal beta-sheets as the primary unfolding steps. The low force resistance of the C-terminal relative to the N-terminal beta-sheet is attributed to their different geometry. A subsequent rearrangement of the autoinhibitory tail is seen to lead to the exposure of the active site, as is required for titin kinase activity. These results support the hypothesis of titin kinase as a force sensor.

Indexed as

Models, ChemicalModels, MolecularComputer SimulationConnectinElasticityEnzyme ActivationMechanicsMuscle ProteinsPhysical StimulationProtein ConformationProtein KinasesStress, MechanicalStructure-Activity RelationshipConnectinMuscle ProteinsProtein Kinases

Identifiers

PMID15531631
PMCPMC1305156
OpenAlexW2160839662

What OpenQuestion holds

Textmetadata
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.