PXD064468 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | HDX-MS studies on human and avian TRPM8 in response to menthol and cold |
| Description | Thermosensitive TRP ion channels enable somatosensory nerve fibers to detect changes in our thermal environment over a wide physiologic range. In mammals, the menthol receptor, TRPM8, is activated by temperatures below ~26ºC and is essential for the perception of cold or chemical cooling agents. A fascinating, yet still unachieved goal is to elucidate structural mechanisms whereby TRPM8 or other thermosensitive channels are gated by changes in ambient temperature. Recent studies using electron cryo-microscopy (cryo-EM) have attempted to address this challenging question but are limited by difficulties in visualizing temperature-evoked conformational substates or assessing the energetic landscape governing gating transitions. Here, we close this gap by using cryo-EM to visualize TRPM8 channels in cellular membranes, where bona fide menthol- and cold-evoked open states are captured. We identify a novel ‘semi-swapped’ architecture in which interdigitation of channel subunits is substantially rearranged following repositioning of the S6 transmembrane helix and elements of the pore region. By combining this structural analysis with thermodynamic measurements using hydrogen-deuterium exchange mass spectrometry (HDX-MS), we are able to pinpoint the pore and TRP helices as key regions undergoing stimulus-evoked conformational dynamics that drive channel gating. Conformational mechanisms associated with activation are validated by comparison of human TRPM8 with the menthol-sensitive, but relatively cold-insensitive avian orthologue. We propose a free energy landscape to explain channel gating by cold or cooling agents. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-03-25 |
| AnnouncementXML | Submission_2026-03-25_10:42:11.528.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Xiaoxuan Lin |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Pagrus major; NCBI TaxID: NEWT:143350; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Q Exactive |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-05-30 21:07:54 | ID requested | |
| ⏵ 1 | 2026-03-25 10:42:12 | announced | |
Publication List
Keyword List
| submitter keyword: HDX-MS, thermosensation, ion channel, TRPM8 |
Contact List
| Yifan Cheng |
|---|
| contact affiliation | Department of Biochemistry and Biophysics, University of California San Franscisco, San Francisco, CA, USA; Howard Hughes Medical Institute |
| contact email | yifan.cheng@ucsf.edu |
| lab head | |
| Xiaoxuan Lin |
|---|
| contact affiliation | Department of Biochemistry and Biophysics, University of California San Francisco |
| contact email | xiaoxuan.lin@ucsf.edu |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/03/PXD064468 |
| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD064468
- Label: PRIDE project
- Name: HDX-MS studies on human and avian TRPM8 in response to menthol and cold
