ArticleScientific reports2019
Different substrate specificities of the two ADPR binding sites in TRPM2 channels of Nematostella vectensis and the role of IDPR.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Analysis of ligand binding and resulting conformational changes in pyrophosphatase NUDT9.The FEBS journal · 2021Article
- Species-Specific Regulation of TRPM2 by PI(4,5)PInternational journal of molecular sciences · 2021Article
- Two Decades of Evolution of Our Understanding of the Transient Receptor Potential Melastatin 2 (TRPM2) Cation Channel.Life (Basel, Switzerland) · 2021Review
- Roles of NADMolecules (Basel, Switzerland) · 2020Review
- Structure-Function Relationship of TRPM2: Recent Advances, Contradictions, and Open Questions.International journal of molecular sciences · 2020Review
- Selective profiling of N- and C-terminal nucleotide-binding sites in a TRPM2 channel.The Journal of general physiology · 2020Article
- TRPM2, linking oxidative stress and CaCurrent opinion in immunology · 2020Review
- Does Cyclic ADP-Ribose (cADPR) Activate the Non-selective Cation Channel TRPM2?Frontiers in immunology · 2020Review
- Synthesis of phosphonoacetate analogues of the second messenger adenosine 5'-diphosphate ribose (ADPR).RSC advances · 2020Article
- A structural overview of the ion channels of the TRPM family.Cell calcium · 2020Review
- Functional importance of NUDT9H domain and N-terminal ADPR-binding pocket in two species variants of vertebrate TRPM2 channels.Scientific reports · 2019Article
- Ligand recognition and gating mechanism through three ligand-binding sites of human TRPM2 channel.eLife · 2019Article
- Synthesis of Terminal Ribose Analogues of Adenosine 5'-Diphosphate Ribose as Probes for the Transient Receptor Potential Cation Channel TRPM2.The Journal of organic chemistry · 2019Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
NvTRPM2 (Nematostella vectensis Transient Receptor Potential Melastatin 2), the species variant of the human apoptosis-related cation channel hTRPM2, is gated by ADP-ribose (ADPR) independently of the C-terminal NUDT9H domain that mediates ADPR-directed gating in hTRPM2. The decisive binding site in NvTRPM2 is likely to be identical with the N-terminal ADPR binding pocket in zebra fish DrTRPM2. Our aim was a characterization of this binding site in NvTRPM2 with respect to its substrate specificity, in comparison to the classical ADPR interaction site within NUDT9H that is highly homologous in hTRPM2 and NvTRPM2, although only in NvTRPM2, catalytic (ADPRase) activity is conserved. With various ADPR analogues, key differences of the two sites were identified. Particularly, two reported antagonists on hTRPM2 were agonists on NvTRPM2. Moreover, IDP-ribose (IDPR) induced currents both in hTRPM2 and NvTRPM2 but not in NvTRPM2 mutants in which NUDT9H was absent. Thus, IDPR acts on NUDT9H rather than N-terminally, revealing a regulatory function of NUDT9H in NvTRPM2 opposed to that in hTRPM2. We propose that IDPR competitively inhibits the ADPRase function of NUDT9H and evokes ADPR accumulation. The findings provide important insights into the structure-function relationship of NvTRPM2 and will allow further characterization of the novel ADPR interaction site.
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