{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T06:09:42Z","timestamp":1771654182724,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,18]]},"group-title":"Biochemistry","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Transient receptor potential melastatin 1 (TRPM1), a Ca\n                  <jats:sup>\u00b2\u207a<\/jats:sup>\n                  -permeable nonselective cation channel essential for retinal ON bipolar cell signaling and night vision, and implicated in congenital night blindness, has remained structurally and functionally poorly characterized. Here we report the first cryo\u2013electron microscopy structure of human TRPM1 in conducting state. Although the channel assembles as a tetramer, it adopts an unexpected clockwise domain-swapped pore module with rotational geometry inverse to that observed in previously characterized 6-TM tetrameric channels. This inverted topology is accompanied by extensive remodeling of the S5\u2013P\u2013S6 module, dilation of the selectivity filter, expansion of the central cavity, and splaying of S6 to form a wide intracellular gate. Single-channel recordings reveal constitutive activity consistent with the conductive state captured. Together, these findings uncover a new 6-TM fold in tetrameric channel and provide a framework for understanding TRPM1 gating and disease-associated dysfunction.\n                <\/jats:p>","DOI":"10.64898\/2026.02.18.706614","type":"posted-content","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T06:20:11Z","timestamp":1771482011000},"source":"Crossref","is-referenced-by-count":0,"title":["Unique pore architecture underlies constitutive gating of human retinal TRPM1"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2358-1844","authenticated-orcid":false,"given":"Mansi","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"},{"name":"Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"KV","family":"Nageswar","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"},{"name":"Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"},{"name":"Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ankur","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"},{"name":"Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sristi","family":"Nanda","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"},{"name":"Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nishtha","family":"Varshney","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"},{"name":"Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohit","family":"Chettri","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"},{"name":"Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9925-7599","authenticated-orcid":false,"given":"Kirill A.","family":"Martemyanov","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Miami Miller School of Medicine; Miami, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2685-4018","authenticated-orcid":false,"given":"Appu Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"},{"name":"Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur; Kanpur, Uttar Pradesh-208016, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026022021450560000_2026.02.18.706614v1.1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/978-3-642-54215-2_15","article-title":"Trpm1","volume":"222","year":"2014","journal-title":"Handb Exp Pharmacol"},{"key":"2026022021450560000_2026.02.18.706614v1.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908711106"},{"key":"2026022021450560000_2026.02.18.706614v1.3","doi-asserted-by":"crossref","unstructured":"T. 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