Evidence map›Paper›PMID 20404344›Full record

ArticleThe Journal of biological chemistry2010

Mapping the ryanodine receptor FK506-binding protein subunit using fluorescence resonance energy transfer.

Razvan L Cornea, Florentin R Nitu, Montserrat Samsó, David D Thomas, Bradley R Fruen

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
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  7. Synergistic FRET assays for drug discovery targeting RyR2 channels.Journal of molecular and cellular cardiology · 2022
    Article
  8. Cellular and Molecular Processes in Pulmonary Hypertension.Advances in experimental medicine and biology · 2021
    Article
  9. Article
  10. Article
  11. Unnatural verticilide enantiomer inhibits type 2 ryanodine receptor-mediated calcium leak and is antiarrhythmic.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  12. Review
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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 2 institutions in 1 country.

Razvan L CorneaDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Florentin R Nitu
Montserrat Samsó
David D Thomas
Bradley R Fruen
University of Minnesota · USBrigham and Women's Hospital · US

Funding

Pathophysiological Regulation of Cardiac Myocyte RyR ChannelR01HL092097 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Donald M Bers, Robyn T Rebbeck · 2010 to 2026
$9.3M
Structural Dynamics of Muscle Calcium ATPase RegulationR01GM027906 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI THOMAS, DAVID D · 1985 to 2016
$8.6M
Molecular interactions regulating RyR Ca2+ channelsR01HL076433 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI FRUEN, BRADLEY R. · 2005 to 2008
$1.4M
NHLBI NIH HHS R01 HL076433NHLBI NIH HHS R01HL076433NHLBI NIH HHS R01 HL092097NHLBI NIH HHS R01HL092097NIGMS NIH HHS R01 GM027906NIGMS NIH HHS R01GM27906
6 · The paper itself

Abstract

The 12-kDa FK506-binding proteins (FKBP12 and FKBP12.6) are regulatory subunits of ryanodine receptor (RyR) Ca(2+) release channels. To investigate the structural basis of FKBP interactions with the RyR1 and RyR2 isoforms, we used site-directed fluorescent labeling of FKBP12.6, ligand binding measurements, and fluorescence resonance energy transfer (FRET). Single-cysteine substitutions were introduced at five positions distributed over the surface of FKBP12.6. Fluorescent labeling at position 14, 32, 49, or 85 did not affect high affinity binding to the RyR1. By comparison, fluorescent labeling at position 41 reduced the affinity of FKBP12.6 binding by 10-fold. Each of the five fluorescent FKBPs retained the ability to inhibit [(3)H]ryanodine binding to the RyR1, although the maximal extent of inhibition was reduced by half when the label was attached at position 32. The orientation of FKBP12.6 bound to the RyR1 and RyR2 was examined by measuring FRET from the different labeling positions on FKBP12.6 to an acceptor attached within the RyR calmodulin subunit. FRET was dependent on the position of fluorophore attachment on FKBP12.6; however, for any given position, the distance separating donors and acceptors bound to RyR1 versus RyR2 did not differ significantly. Our results show that FKBP12.6 binds to RyR1 and RyR2 in the same orientation and suggest new insights into the discrete structural domains responsible for channel binding and inhibition. FRET mapping of RyR-bound FKBP12.6 is consistent with the predictions of a previous cryoelectron microscopy study and strongly supports the proposed structural model.

Indexed as

AnimalsCalmodulinFluorescence Resonance Energy TransferHumansImmunophilinsMuscle, SkeletalMutationMyocardiumProtein BindingProtein Structure, TertiaryRyanodineRyanodine Receptor Calcium Release ChannelSarcoplasmic ReticulumSwineTacrolimus Binding ProteinsCalmodulinImmunophilinsRyanodineRyanodine Receptor Calcium Release ChannelTacrolimus Binding Proteins

Identifiers

PMID20404344
PMCPMC2885200
OpenAlexW2143210433

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.