{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:23:20Z","timestamp":1792131800604,"version":"4.4.0"},"reference-count":58,"publisher":"National Academy of Sciences","issue":"50","license":[{"start":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T00:00:00Z","timestamp":1558396800000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100006221","name":"United States - Israel Binational Science Foundation","doi-asserted-by":"publisher","award":["2015221"],"award-info":[{"award-number":["2015221"]}],"id":[{"id":"10.13039\/100006221","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["16SDG26700010"],"award-info":[{"award-number":["16SDG26700010"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1444\/16"],"award-info":[{"award-number":["1444\/16"]}],"id":[{"id":"10.13039\/501100003977","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":[[2018,12,11]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>The TRPV1 channel integrates noxious stimuli from multiple sources to evoke an appropriate pain response. However, while different stimuli evoke distinct channel activation, the underlying molecular mechanisms remain unclear. Here, we aim at elucidating the structural determinants that regulate the different TRPV1 responses to two toxins: capsaicin and double-knot toxin (DkTx). We found that the channel pore turret domain imposes two opposite effects on the responses to these toxins. While it restricts the ion conductance of the DkTx-evoked current, it stabilizes the open channel state evoked by capsaicin. Together, our results indicate that TRPV1 pore turret dictates different gating mechanisms in response to agonists acting through different binding domains.<\/jats:p>","DOI":"10.1073\/pnas.1809662115","type":"journal-article","created":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T14:06:22Z","timestamp":1542809182000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":51,"title":["TRPV1 pore turret dictates distinct DkTx and capsaicin gating"],"prefix":"10.1073","volume":"115","author":[{"given":"Matan","family":"Geron","sequence":"first","affiliation":[{"name":"The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Karem, 9112102 Jerusalem, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Karem, 9112102 Jerusalem, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Theoretical Molecular Biophysics Laboratory, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 D.","family":"Faraldo-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Theoretical Molecular Biophysics Laboratory, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-1534","authenticated-orcid":false,"given":"Valeria","family":"V\u00e1squez","sequence":"additional","affiliation":[{"name":"Department of Physiology, The University of Tennessee Health Science Center, Memphis, TN 38163"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6105-5035","authenticated-orcid":false,"given":"Avi","family":"Priel","sequence":"additional","affiliation":[{"name":"The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Karem, 9112102 Jerusalem, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2018,11,21]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2012.04.336"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2014.07.027"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/2049463713502005"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.06.001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins5122533"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/39807"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.12.016"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.109.055624"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2013.05.016"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.100129497"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201601132R"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05285"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.03.052"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9297"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins7093671"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2017.01.004"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi035981h"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1835"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00171"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05339-6"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.11273"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2004.02.005"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12823"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17964"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051516"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.13356"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00757-2"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.11.005"},{"key":"e_1_3_3_29_2","first-page":"1","article-title":"Mechanosensation","author":"Goodman M","year":"2006","unstructured":"M Goodman, Mechanosensation. WormBook, pp. 1\u201314 (2006).","journal-title":"WormBook"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-101011-155833"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12822"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.top066050"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000357107"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201110724"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.77.062906.171838"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1517288113"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c120001"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-9-30"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2552"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201311024"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10426-7"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi051494l"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.3390\/md14120229"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200910255"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.10.063"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins9100326"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.28626"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1700810"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063865"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/77.1.71"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1865"},{"key":"e_1_3_3_52_2","first-page":"1","article-title":"Behavior","volume":"871","author":"Hart A","year":"2006","unstructured":"A Hart, Behavior. WormBook 871, 1\u201367 (2006).","journal-title":"WormBook"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep12278"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-10-03525.1997"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0809-551"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20817"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0263-7855(97)00009-X"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.190611"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1809662115","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1809662115","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T03:30:43Z","timestamp":1649820643000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1809662115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,21]]},"references-count":58,"journal-issue":{"issue":"50","published-print":{"date-parts":[[2018,12,11]]}},"alternative-id":["10.1073\/pnas.1809662115"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1809662115","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,21]]},"assertion":[{"value":"2018-11-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}