Evidence map›Paper›PMID 25404341›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Activity-regulating structural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange.

Rasmus Iversen, Simon Mysling, Kathrin Hnida, Thomas J D Jørgensen, Ludvig M Sollid

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 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
5.4field-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

24 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
  2. Review
  3. The Impact ofInternational journal of molecular sciences · 2023
    Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Efficient T cell-B cell collaboration guides autoantibody epitope bias and onset of celiac disease.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. TheThe Journal of biological chemistry · 2018
    Article
  15. Optimization of Feasibility Stage for Hydrogen/Deuterium Exchange Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2018
    Article
  16. An isomerase completes the circuit for a redox switch.The Journal of biological chemistry · 2018
    Article
  17. Article
  18. Conformational dynamics of a neurotransmitter:sodium symporter in a lipid bilayer.Proceedings of the National Academy of Sciences of the United States of America · 2017
    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

5 authors at 3 institutions in 2 countries.

Rasmus IversenCentre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital, N-0372 Oslo, Norway; and.
Simon MyslingDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5320 Odense M, Denmark.
Kathrin HnidaCentre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital, N-0372 Oslo, Norway; and.
Thomas J D JørgensenDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5320 Odense M, Denmark l.m.sollid@medisin.uio.no tjdj@bmb.sdu.dk.
Ludvig M SollidCentre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital, N-0372 Oslo, Norway; and l.m.sollid@medisin.uio.no tjdj@bmb.sdu.dk.
Oslo University Hospital · NOUniversity of Southern Denmark · DKUniversity of Oslo · NO

Funding

European Research Council 268541
6 · The paper itself

Abstract

The multifunctional enzyme transglutaminase 2 (TG2) is the target of autoantibodies in the gluten-sensitive enteropathy celiac disease. In addition, the enzyme is responsible for deamidation of gluten peptides, which are subsequently targeted by T cells. To understand the regulation of TG2 activity and the enzyme's role as an autoantigen in celiac disease, we have addressed structural properties of TG2 in solution by using hydrogen/deuterium exchange monitored by mass spectrometry. We demonstrate that Ca(2+) binding, which is necessary for TG2 activity, induces structural changes in the catalytic core domain of the enzyme. Cysteine oxidation was found to abolish these changes, suggesting a mechanism whereby disulfide bond formation inactivates the enzyme. Further, by using TG2-specific human monoclonal antibodies generated from intestinal plasma cells of celiac disease patients, we observed that binding of TG2 by autoantibodies can induce structural changes that could be relevant for the pathogenesis. Detailed mapping of two of the main epitopes targeted by celiac disease autoantibodies revealed that they are located adjacent to each other in the N-terminal part of the TG2 molecule.

Indexed as

AutoantibodiesBinding SitesCalciumCeliac DiseaseDeuterium Exchange MeasurementDisulfidesElectrophoresis, Polyacrylamide GelEpitope MappingEpitopesGTP-Binding ProteinsHumansIntestinal MucosaIntestinesMass SpectrometryModels, MolecularMolecular Sequence DataAutoantibodiesCalciumDisulfidesEpitopesGTP-Binding ProteinsProtein Glutamine gamma Glutamyltransferase 2Transglutaminasesautoantibodiesceliac diseasehydrogen/deuterium exchangetransglutaminase 2

Identifiers

PMID25404341
PMCPMC4260576
OpenAlexW2014996172

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.