Evidence map›Paper›PMID 24001019›Full record

ArticleThe Biochemical journal2013

Human junctophilin-2 undergoes a structural rearrangement upon binding PtdIns(3,4,5)P3 and the S101R mutation identified in hypertrophic cardiomyopathy obviates this response.

Hayley J Bennett, John Bernard Davenport, Richard F Collins, Andrew W Trafford, Christian Pinali, Ashraf Kitmitto

Open access · hybridAbstract read
In one paragraph

Article in The Biochemical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.0field-weighted citation impact, top 21% 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

29 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Cardiac Cell Remodeling in Obesity and Diabetes.Handbook of experimental pharmacology · 2026
    Review
  3. Nonstructural Roles of Junctophilin-2 in the Heart.JACC. Basic to translational science · 2025
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Activation of CaMolecular and cellular biochemistry · 2024
    Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Structures of the junctophilin/voltage-gated calcium channel interface reveal hot spot for cardiomyopathy mutations.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  17. Review
  18. Article
  19. Review
  20. Targeting JP2: A New Treatment for Pulmonary Hypertension.Oxidative medicine and cellular longevity · 2021
    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

6 authors at 1 institution in 1 country.

Hayley J Bennett*Institute of Cardiovascular Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9NT, U.K.
John Bernard Davenport
Richard F Collins
Andrew W Trafford
Christian Pinali
Ashraf Kitmitto
University of Manchester · GB

Funding

British Heart Foundation FS/12/57/29717British Heart Foundation RG/11/2/28701
6 · The paper itself

Abstract

JP2 (junctophilin-2) is believed to hold the transverse tubular and jSR (junctional sarcoplasmic reticulum) membranes in a precise geometry that facilitates excitation-contraction coupling in cardiomyocytes. We have expressed and purified human JP2 and shown using electron microscopy that the protein forms elongated structures ~15 nm long and 2 nm wide. Employing lipid-binding assays and quartz crystal microbalance with dissipation we have determined that JP2 is selective for PS (phosphatidylserine), with a Kd value of ~0.5 μM, with the N-terminal domain mediating this interaction. JP2 also binds PtdIns(3,4,5)P3 at a different site than PS, resulting in the protein adopting a more flexible conformation; this interaction is modulated by both Ca(2+) and Mg(2+) ions. We show that the S101R mutation identified in patients with hypertrophic cardiomyopathy leads to modification of the protein secondary structure, forming a more flexible molecule with an increased affinity for PS, but does not undergo a structural transition in response to binding PtdIns(3,4,5)P3. In conclusion, the present study provides new insights into the structural and lipid-binding properties of JP2 and how the S101R mutation may have an effect upon the stability of the dyad organization with the potential to alter JP2-protein interactions regulating Ca(2+) cycling.

Indexed as

Mutation, MissenseBinding SitesCalciumCardiomyopathy, Hypertrophic, FamilialHumansMagnesiumMembrane ProteinsPhosphatidylinositol PhosphatesPhospholipidsProtein BindingProtein StabilityProtein Structure, SecondaryProtein Structure, TertiaryQuartz Crystal Microbalance TechniquesThermodynamicsCalciumjunctophilinMagnesiumMembrane Proteinsphosphatidylinositol 3,4,5-triphosphatePhosphatidylinositol PhosphatesPhospholipids

Identifiers

PMID24001019
PMCPMC3898329
OpenAlexW2060470202

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.