ArticleScience (New York, N.Y.)2019
Structural insights into TRPM8 inhibition and desensitization.
Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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The trial behind it
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Who cites it
104 citing papers in PubMed, 173 citations in OpenAlex.
- Molecular basis for cold and menthol sensing by mammalian TRPM8.Nature communications · 2026Article
- Symmetry-driven gating of TRPM8 by PIPNature communications · 2026Article
- Temperature and intrinsic CaNature structural & molecular biology · 2026Article
- Structural energetics of cold sensitivity.Nature · 2026Article
- Deep mutational scan of the pore of the cold-sensing TRPM8 channel.bioRxiv : the preprint server for biology · 2026Article
- Sialylation in the nervous system: Functions and mechanisms.The Journal of biological chemistry · 2026Review
- A single allosteric site merges activation, modulation and inhibition in TRPM5.Nature chemical biology · 2026Article
- Rewiring melanoma cell fate: TRPM8 modulators trigger apoptosis and boost NK cell cytotoxicity.Cell death & disease · 2026Article
- Rational tuning of temperature sensitivity of the TRPM8 channel.EMBO reports · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Direct modulation of TRPM8 ion channels by rapamycin and analog macrolide immunosuppressants.eLife · 2025Article
- The structural basis of cold sensitivity.bioRxiv : the preprint server for biology · 2025Article
- TRPM8 Protein Dynamics Correlates with Ligand Structure and Cellular Function.Journal of the American Chemical Society · 2025Article
- TRPM8 protein dynamics correlates with ligand structure and cellular function.bioRxiv : the preprint server for biology · 2025Article
- Molecular basis of neurosteroid and anticonvulsant regulation of TRPM3.Nature structural & molecular biology · 2025Article
- Forty sites of TRP channel regulation.Current opinion in chemical biology · 2025Review
- Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders.The Journal of membrane biology · 2024Article
- Article
- Ion channels of cold transduction and transmission.The Journal of general physiology · 2024Review
- Navigating the Controversies: Role of TRPM Channels in Pain States.International journal of molecular sciences · 2024Review
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The transient receptor potential melastatin 8 (TRPM8) ion channel is the primary detector of environmental cold and an important target for treating pathological cold hypersensitivity. Here, we present cryo-electron microscopy structures of TRPM8 in ligand-free, antagonist-bound, or calcium-bound forms, revealing how robust conformational changes give rise to two nonconducting states, closed and desensitized. We describe a malleable ligand-binding pocket that accommodates drugs of diverse chemical structures, and we delineate the ion permeation pathway, including the contribution of lipids to pore architecture. Furthermore, we show that direct calcium binding mediates stimulus-evoked desensitization, clarifying this important mechanism of sensory adaptation. We observe large rearrangements within the S4-S5 linker that reposition the S1-S4 and pore domains relative to the TRP helix, leading us to propose a distinct model for modulation of TRPM8 and possibly other TRP channels.
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Registered trials
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.