{
  "abstract": "The transient receptor potential melastatin member 8 (TRPM8) is a polymodal ion channel that senses cold and menthol in mammals. Despite prior structural studies, the mechanisms by which cold and menthol activate TRPM8 remain unresolved. Here, we present cryo-EM structures representing the cold and menthol-dependent activation trajectories, combined with extensive functional analyses. We captured snapshots of cooling-dependent pore opening, which involves dramatic pore rearrangement, suggesting a mechanism for cold sensing. Moreover, menthol binds dynamically to induce channel activation, which may underlie menthol specificity for TRPM8. Finally, we show how TRPM8 integrates multiple modalities (cold and menthol) through overlapping but non-identical pathways, revealing the temperature-specific “cold spot”. These findings enhance our understanding of the molecular basis of physically and chemically induced cool sensation in mammals.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biochemistry, Duke University School of Medicine, Durham, NC, USA",
    "Genome Integrity and Structural Biology Laboratory, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, USA",
    "Department of Biochemistry, Duke University School of Medicine, Durham, NC, USA. seok-yong.lee@duke.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hyuk-Joon Lee",
      "orcid": "0000-0001-7568-2307"
    },
    {
      "affs": [
        0
      ],
      "name": "Cheon-Gyu Park",
      "orcid": "0000-0002-4739-1913"
    },
    {
      "affs": [
        0
      ],
      "name": "Justin G. Fedor",
      "orcid": "0000-0003-3660-3818"
    },
    {
      "affs": [
        1
      ],
      "name": "Wyatt A. Peele",
      "orcid": "0009-0007-9706-9280"
    },
    {
      "affs": [
        1
      ],
      "name": "Mario Juan Borgnia",
      "orcid": "0000-0001-9159-1413"
    },
    {
      "affs": [
        2
      ],
      "name": "Seok‐Yong Lee",
      "orcid": "0000-0002-0662-9921"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5yfkmm20smg98.bib",
  "cited_by": 7,
  "doi": "10.1038/s41467-026-76926-1",
  "fulltext_url": null,
  "id": "5yfkmm20smg98",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-76926-1",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2809|Ion Channels and Receptors"
    ]
  ],
  "openalex": "W7203610322",
  "pdf_url": null,
  "pmcid": "PMC12440020",
  "pmid": "40964340",
  "published": "2026-08-17",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/5yfkmm20smg98.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T13:21:01Z",
      "native_id": "W7203610322",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-76926-1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2809|Ion Channels and Receptors",
      "subfield": "neuroscience"
    }
  ],
  "title": "Molecular basis for cold and menthol sensing by mammalian TRPM8",
  "title_text": "Molecular basis for cold and menthol sensing by mammalian TRPM8",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:12Z",
  "url": "https://research.draconitic.com/paper/5yfkmm20smg98",
  "venue": "Nature Communications",
  "versions": []
}