Evidence map›Paper›PMID 27383051›Full record

ArticleeLife2016

The proposed channel-enzyme transient receptor potential melastatin 2 does not possess ADP ribose hydrolase activity.

Iordan Iordanov, Csaba Mihályi, Balázs Tóth, László Csanády

Open access · goldAbstract read
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
5.5field-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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
  2. CaCommunications biology · 2026
    Article
  3. Article
  4. Review
  5. A conserved mechanism couples cytosolic domain movements to pore gating in the TRPM2 channel.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  6. Article
  7. The odyssey of the TR(i)P journey to the cellular membrane.Frontiers in cell and developmental biology · 2024
    Review
  8. Role of TRP Channels in Liver-Related Diseases.International journal of molecular sciences · 2023
    Review
  9. Molecular dynamics study of ClCellular and molecular life sciences : CMLS · 2023
    Article
  10. Large-scale proteomic analysis ofFrontiers in parasitology · 2023
    Article
  11. Review
  12. Review
  13. The crystal structure of TRPM2 MHR1/2 domain reveals a conserved ZnProtein science : a publication of the Protein Society · 2022
    Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Roles of NADMolecules (Basel, Switzerland) · 2020
    Review
  19. Review
  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

4 authors at 1 institution in 1 country.

Iordan IordanovDepartment of Medical Biochemistry, Semmelweis University, Budapest, Hungary.ORCID 0000-0001-8251-5857
Csaba MihályiDepartment of Medical Biochemistry, Semmelweis University, Budapest, Hungary.ORCID 0000-0001-7536-3066
Balázs TóthDepartment of Medical Biochemistry, Semmelweis University, Budapest, Hungary.
László CsanádyDepartment of Medical Biochemistry, Semmelweis University, Budapest, Hungary.ORCID 0000-0002-6547-5889
Semmelweis University · HU

Funding

Howard Hughes Medical Institute 55007416
6 · The paper itself

Abstract

Transient Receptor Potential Melastatin 2 (TRPM2) is a Ca(2+)-permeable cation channel essential for immunocyte activation, insulin secretion, and postischemic cell death. TRPM2 is activated by ADP ribose (ADPR) binding to its C-terminal cytosolic NUDT9-homology (NUDT9H) domain, homologous to the soluble mitochondrial ADPR pyrophosphatase (ADPRase) NUDT9. Reported ADPR hydrolysis classified TRPM2 as a channel-enzyme, but insolubility of isolated NUDT9H hampered further investigations. Here we developed a soluble NUDT9H model using chimeric proteins built from complementary polypeptide fragments of NUDT9H and NUDT9. When expressed in E.coli, chimeras containing up to ~90% NUDT9H sequence remained soluble and were affinity-purified. In ADPRase assays the conserved Nudix-box sequence of NUDT9 proved essential for activity (kcat~4-9s(-1)), that of NUDT9H did not support catalysis. Replacing NUDT9H in full-length TRPM2 with soluble chimeras retained ADPR-dependent channel gating (K1/2~1-5 μM), confirming functionality of chimeric domains. Thus, TRPM2 is not a 'chanzyme'. Chimeras provide convenient soluble NUDT9H models for structural/biochemical studies.

Indexed as

Adenosine Diphosphate RiboseEscherichia coliGene ExpressionHumansHydrolasesProtein BindingRecombinant ProteinsTRPM Cation ChannelsAdenosine Diphosphate RiboseHydrolasesRecombinant ProteinsTRPM2 protein, humanTRPM Cation ChannelsADPRbiochemistrybiophysicschanzymechimeraE. coliNUDT9H domainstructural biologyTRPM2xenopus

Identifiers

PMID27383051
PMCPMC4974056
OpenAlexW2466048253

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.