{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T17:12:12Z","timestamp":1774804332638,"version":"3.50.1"},"reference-count":40,"publisher":"Proceedings of the National Academy of Sciences","issue":"46","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"EU Horizon 2020 Research and Innovation Program","award":["739593"],"award-info":[{"award-number":["739593"]}]},{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"publisher","award":["KKP_22 144199"],"award-info":[{"award-number":["KKP_22 144199"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"MOST | National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA1302300"],"award-info":[{"award-number":["2021YFA1302300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32171201"],"award-info":[{"award-number":["32171201"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hungarian Academy of Sciences Bolyai Research Scholarship","award":["BO\/00685\/22"],"award-info":[{"award-number":["BO\/00685\/22"]}]},{"name":"Ministry of Human Capacities of Hungary","award":["\u00daNKP-23-5-SE-21"],"award-info":[{"award-number":["\u00daNKP-23-5-SE-21"]}]},{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"publisher","award":["FK-138576"],"award-info":[{"award-number":["FK-138576"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,11,12]]},"abstract":"<jats:p>\n            Transient Receptor Potential Melastatin 2 (TRPM2) cation channels contribute to immunocyte activation, insulin secretion, and central thermoregulation. TRPM2 opens upon binding cytosolic Ca\n            <jats:sup>2+<\/jats:sup>\n            and ADP ribose (ADPR). We present here the 2.5 \u00c5 cryo-electronmicroscopy structure of TRPM2 from\n            <jats:italic>Nematostella vectensis<\/jats:italic>\n            (nvTRPM2) in a lipid nanodisc, complexed with Ca\n            <jats:sup>2+<\/jats:sup>\n            and ADPR-2\u2032-phosphate. Comparison with nvTRPM2 without nucleotide reveals that nucleotide binding-induced movements in the protein\u2019s three \u201ccore\u201d layers deconvolve into a set of rigid-body rotations conserved from cnidarians to man. By covalently crosslinking engineered cysteine pairs we systematically trap the cytosolic layers in specific conformations and study effects on gate opening\/closure. The data show that nucleotide binding in Layer 3 disrupts inhibitory intersubunit interactions, allowing rotation of Layer 2 which in turn expands the gate located in Layer 1. Channels trapped in that \u201cactivated\u201d state are no longer nucleotide dependent, but are opened by binding of Ca\n            <jats:sup>2+<\/jats:sup>\n            alone.\n          <\/jats:p>","DOI":"10.1073\/pnas.2415548121","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T16:44:53Z","timestamp":1731084293000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":9,"title":["A conserved mechanism couples cytosolic domain movements to pore gating in the TRPM2 channel"],"prefix":"10.1073","volume":"121","author":[{"given":"Bal\u00e1zs","family":"T\u00f3th","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Semmelweis University, Budapest H-1094, Hungary"},{"name":"Molecular Channelopathies Research Group, Hungarian Centre of Excellence for Molecular Medicine - Semmelweis University, Budapest H-1094, Hungary"},{"name":"Ion Channel Research Group, Hungarian Research Network - Semmelweis University, Budapest H-1094, Hungary"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3985-2027","authenticated-orcid":false,"given":"Yuefeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5570-4609","authenticated-orcid":false,"given":"Andras","family":"Szollosi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Semmelweis University, Budapest H-1094, Hungary"},{"name":"Molecular Channelopathies Research Group, Hungarian Centre of Excellence for Molecular Medicine - Semmelweis University, Budapest H-1094, Hungary"},{"name":"Ion Channel Research Group, Hungarian Research Network - Semmelweis University, Budapest H-1094, Hungary"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4932-4343","authenticated-orcid":false,"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China"},{"name":"School of Life Sciences, Peking University, Beijing 100871, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6547-5889","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Csan\u00e1dy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Semmelweis University, Budapest H-1094, Hungary"},{"name":"Molecular Channelopathies Research Group, Hungarian Centre of Excellence for Molecular Medicine - Semmelweis University, Budapest H-1094, Hungary"},{"name":"Ion Channel Research Group, Hungarian Research Network - Semmelweis University, Budapest H-1094, Hungary"}]}],"member":"341","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/35079100"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062473"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210810200"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200810109"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1204702109"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5551"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/10799890600637506"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601083"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1758"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010678108"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-88224-5"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0276"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf7537"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.10.001"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature19074"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.02.035"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2024.102850"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.034561"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.162289"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03396.x"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6318"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808218105"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-024-01316-4"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.36409"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0558-4"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.50175"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.44556"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.17600"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158060"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201912533"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav4809"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201511377"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20253"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP283350"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1294357"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(09)64011-8"},{"key":"e_1_3_4_37_2","author":"Jiang Y.","unstructured":"Y. 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