ArticleNature communications2020
Molecular mechanisms underlying menthol binding and activation of TRPM8 ion channel.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 101 citations in OpenAlex.
- Effects of carbohydrate-electrolyte solutions with and without L-menthol on hydration and performance recovery following simulated firefighting exercise.Journal of the International Society of Sports Nutrition · 2026Trial
- Menthol-induced activation of TRPM8 receptors increases cutaneous blood flow across the dermatome.Microvascular research · 2022Trial
- Effects of a soluble essential oil additive on inflammatory response, epithelial integrity, and performance of broilers subjected to an experimental infectious bronchitis virus challenge.Poultry science · 2026Article
- Molecular basis for cold and menthol sensing by mammalian TRPM8.Nature communications · 2026Article
- DangGuiSiNi Decoction and QiShenYiQi Pills Ameliorate Hyperpermeability and Edema Induced by Cold Exposure.Microcirculation (New York, N.Y. : 1994) · 2026Article
- Symmetry-driven gating of TRPM8 by PIPNature communications · 2026Article
- Article
- Temperature-Dependent Menthol Binding across TRPM8 Conformational States.Journal of the American Chemical Society · 2026Article
- Wired for immunity: neuroimmune control of the lung by sensory neurons.Nature reviews. Neuroscience · 2026Review
- Conformational Fingerprints Underlying Thermal Modulation of PAC/TMEM206 Gating.International journal of molecular sciences · 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
- (-)-Englerin A binding to human TRPC5 exposes an aromatic interaction network in channel activation.Nature communications · 2026Article
- Menthol-induced sedation and hemodynamic safety limits in Nile tilapia: defining a therapeutic window.Fish physiology and biochemistry · 2026Article
- Efficacy of menthol on cell viability of lung cancer cell line (A549): bioinformatics study and effect on the expression of the tumor suppressor gene p53.Journal of applied genetics · 2026Article
- Rewiring melanoma cell fate: TRPM8 modulators trigger apoptosis and boost NK cell cytotoxicity.Cell death & disease · 2026Article
- The tip of the iceberg: Profiling cooling agents using computational approaches to inform tobacco regulatory science.PloS one · 2026Article
- Cooling sensation biosensor coupled with the Chou-Talalay method for quantitative assessment of interaction patterns in binary cooling agent mixtures.Current research in food science · 2026Article
- Modulation of corneal sensory processing and pain responses by dry eye and corneal wounding.Frontiers in cellular neuroscience · 2026Article
- Gut Microbiota and Liver Metabolism Regulation Mediate the Protective Effects of Inactivated Selenium-Enriched Yeast Against Alcohol-Induced Liver Damage in Mice.Foods (Basel, Switzerland) · 2025Article
2 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
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Menthol in mints elicits coolness sensation by selectively activating TRPM8 channel. Although structures of TRPM8 were determined in the apo and liganded states, the menthol-bounded state is unresolved. To understand how menthol activates the channel, we docked menthol to the channel and systematically validated our menthol binding models with thermodynamic mutant cycle analysis. We observed that menthol uses its hydroxyl group as a hand to specifically grab with R842, and its isopropyl group as legs to stand on I846 and L843. By imaging with fluorescent unnatural amino acid, we found that menthol binding induces wide-spread conformational rearrangements within the transmembrane domains. By Φ analysis based on single-channel recordings, we observed a temporal sequence of conformational changes in the S6 bundle crossing and the selectivity filter leading to channel activation. Therefore, our study suggested a 'grab and stand' mechanism of menthol binding and how menthol activates TRPM8 at the atomic level.
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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.