ArticleThe Journal of general physiology2017
Identification of the ADPR binding pocket in the NUDT9 homology domain of TRPM2.
Article in The Journal of general physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 54 citations in OpenAlex.
- Domain-Specific Agonist Binding Affinities Explain Structural and Functional Regulation of TRPM2.bioRxiv : the preprint server for biology · 2026Article
- Coupling enzymatic activity and gating in an ancient TRPM chanzyme and its molecular evolution.Nature structural & molecular biology · 2024Article
- Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury.Frontiers in immunology · 2024Review
- Interaction of Calmodulin with TRPM: An Initiator of Channel Modulation.International journal of molecular sciences · 2023Review
- Use the force, fluke: Ligand-independent gating of Schistosoma mansoni ion channel TRPMInternational journal for parasitology · 2023Article
- Role of PARP and TRPM2 in VEGF Inhibitor-Induced Vascular Dysfunction.Journal of the American Heart Association · 2023Article
- Large-scale proteomic analysis ofFrontiers in parasitology · 2023Article
- TRPM2 Mediates Hepatic Ischemia-Reperfusion Injury via CaResearch (Washington, D.C.) · 2023Article
- Pathological Mechanisms Induced by TRPM2 Ion Channels Activation in Renal Ischemia-Reperfusion Injury.Molecular biology reports · 2022Review
- Artemisinin inhibits neutrophil and macrophage chemotaxis, cytokine production and NET release.Scientific reports · 2022Article
- The identification of the key residues E829 and R845 involved in transient receptor potential melastatin 2 channel gating.Frontiers in aging neuroscience · 2022Article
- The Antibody Receptor Fc Gamma Receptor IIIb Induces Calcium EntryFrontiers in immunology · 2021Article
- Vascular Dysfunction in Diabetes and Obesity: Focus on TRP Channels.Frontiers in physiology · 2021Review
- Roles of NADMolecules (Basel, Switzerland) · 2020Review
- TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions.Redox biology · 2020Review
- Structure-Function Relationship of TRPM2: Recent Advances, Contradictions, and Open Questions.International journal of molecular sciences · 2020Review
- The N-terminal domain in TRPM2 channel is a conserved nucleotide binding site.The Journal of general physiology · 2020Article
- Selective profiling of N- and C-terminal nucleotide-binding sites in a TRPM2 channel.The Journal of general physiology · 2020Article
- Characterization and Optimization of the Novel Transient Receptor Potential Melastatin 2 Antagonist tatM2NX.Molecular pharmacology · 2020Article
- TRPM2 channel: A novel target for alleviating ischaemia-reperfusion, chronic cerebral hypo-perfusion and neonatal hypoxic-ischaemic brain damage.Journal of cellular and molecular medicine · 2020Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the transient receptor potential melastatin 2 (TRPM2) channel occurs during the response to oxidative stress under physiological conditions as well as in pathological processes such as ischemia and diabetes. Accumulating evidence indicates that adenosine diphosphate ribose (ADPR) is the most important endogenous ligand of TRPM2. However, although it is known that ADPR binds to the NUDT9 homology (NUDT9-H) domain in the intracellular C-terminal region, the molecular mechanism underlying ADPR binding and activation of TRPM2 remains unknown. In this study, we generate a structural model of the NUDT9-H domain and identify the binding pocket for ADPR using induced docking and molecular dynamics simulation. We find a subset of 11 residues-H1346, T1347, T1349, L1379, G1389, S1391, E1409, D1431, R1433, L1484, and H1488-that are most likely to directly interact with ADPR. Results from mutagenesis and electrophysiology approaches support the predicted binding mechanism, indicating that ADPR binds tightly to the NUDT9-H domain, and suggest that the most significant interactions are the van der Waals forces with S1391 and L1484, polar solvation interaction with E1409, and electronic interactions (including π-π interactions) with H1346, T1347, Y1349, D1431, and H1488. These findings not only clarify the roles of a range of newly identified residues involved in ADPR binding in the TRPM2 channel, but also reveal the binding pocket for ADPR in the NUDT9-H domain, which should facilitate structure-based drug design for the TRPM2 channel.
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