ArticleThe Journal of general physiology2020
Selective profiling of N- and C-terminal nucleotide-binding sites in a TRPM2 channel.
Article in The Journal of general physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 26 citations in OpenAlex.
- Direct Assessment of Temperature Sensitivity of the TRPM2 Channel with the Patch Clamp Technique.Methods in molecular biology (Clifton, N.J.) · 2025Article
- 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 · 2024Article
- Coupling enzymatic activity and gating in an ancient TRPM chanzyme and its molecular evolution.Nature structural & molecular biology · 2024Article
- Evolution of Sensory Receptors.Annual review of cell and developmental biology · 2024Review
- Functional characterization of the transient receptor potential melastatin 2 (TRPM2) cation channel from Nematostella vectensis reconstituted into lipid bilayer.Scientific reports · 2023Article
- Dual amplification strategy turns TRPM2 channels into supersensitive central heat detectors.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The crystal structure of TRPM2 MHR1/2 domain reveals a conserved ZnProtein science : a publication of the Protein Society · 2022Article
- Review
- cADPR Does Not Activate TRPM2.International journal of molecular sciences · 2022Article
- 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
- Structure-Function Relationship of TRPM2: Recent Advances, Contradictions, and Open Questions.International journal of molecular sciences · 2020Review
- Transient receptor potential channels: current perspectives on evolution, structure, function and nomenclature.Proceedings. Biological sciences · 2020Article
- The N-terminal domain in TRPM2 channel is a conserved nucleotide binding site.The Journal of general physiology · 2020Article
- Does Cyclic ADP-Ribose (cADPR) Activate the Non-selective Cation Channel TRPM2?Frontiers in immunology · 2020Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transient receptor potential melastatin 2 (TRPM2) is a homotetrameric Ca2+-permeable cation channel important for the immune response, body temperature regulation, and insulin secretion, and is activated by cytosolic Ca2+ and ADP ribose (ADPR). ADPR binds to two distinct locations, formed by large N- and C-terminal cytosolic domains, respectively, of the channel protein. In invertebrate TRPM2 channels, the C-terminal site is not required for channel activity but acts as an active ADPR phosphohydrolase that cleaves the activating ligand. In vertebrate TRPM2 channels, the C-terminal site is catalytically inactive but cooperates with the N-terminal site in channel activation. The precise functional contributions to channel gating and the nucleotide selectivities of the two sites in various species have not yet been deciphered. For TRPM2 of the sea anemone Nematostella vectensis (nvTRPM2), catalytic activity is solely attributable to the C-terminal site. Here, we show that nvTRPM2 channel gating properties remain unaltered upon deletion of the C-terminal domain, indicating that the N-terminal site is single-handedly responsible for channel gating. Exploiting such functional independence of the N- and C-terminal sites, we selectively measure their affinity profiles for a series of ADPR analogues, as reflected by apparent affinities for channel activation and catalysis, respectively. Using site-directed mutagenesis, we confirm that the same N-terminal site observed in vertebrate TRPM2 channels was already present in ancient cnidarians. Finally, by characterizing the functional effects of six amino acid side chain truncations in the N-terminal site, we provide first insights into the mechanistic contributions of those side chains to TRPM2 channel gating.
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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.