{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T12:27:58Z","timestamp":1776774478594,"version":"3.51.2"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u2010RS\u20102023\u201000254795"],"award-info":[{"award-number":["NRF\u2010RS\u20102023\u201000254795"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102024\u20100035110"],"award-info":[{"award-number":["RS\u20102024\u20100035110"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003693","name":"Korea Institute of Science and Technology","doi-asserted-by":"publisher","award":["2E33721"],"award-info":[{"award-number":["2E33721"]}],"id":[{"id":"10.13039\/501100003693","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Tentonin 3 (TTN3\/TMEM150C) is a mechanosensitive ion channel that plays critical roles in mechanotransduction processes. TTN3 forms a tetramer with a predicted rectangular shape and a central pore. A conotoxin \u03c1\u2010TIA and its synthetic analog, noxious mechanosensation blocker 1 (NMB\u20101), were initially developed to inhibit\n                      <jats:bold>slowly adapting (SA)<\/jats:bold>\n                      \u2010type\n                      <jats:bold>mechanically activated (MA)<\/jats:bold>\n                      currents in dorsal root ganglion (DRG) neurons. Since TTN3 confers slowly\u2010adapting MA currents in DRG neurons, both NMB\u20101 and \u03c1\u2010TIA were hypothesized to inhibit TTN3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>To record MA currents, a few micrometre step indentations were applied to HEK cells expressing TTN3. NMB\u20101 and \u03c1\u2010TIA were applied to these cells to test their specific antagonism. Mutations of the conopeptides and TTN3 were made to identify underlying mechanisms of inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      NMB\u20101 strongly inhibited TTN3, whereas \u03c1\u2010TIA had only a weak effect, and neither peptide affected Piezo channels. Alanine\u2010scanning mutagenesis coupled with electrophysiological assays pinpointed that a positively charged residue in NMB\u20101 and \u03c1\u2010TIA is essential for their inhibitory action. Additionally, a glutamate residue (Glu126) near the pore entrance of TTN3 was identified as critical for\n                      <jats:bold>the<\/jats:bold>\n                      NMB\u20101 inhibitory action, suggesting a key electrostatic interaction between NMB\u20101 and TTN3. Molecular dynamics simulations further supported this electrostatic interaction between the peptide ligand and the channel protein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>NMB\u20101 specifically blocks a mechanosensitive channel, TTN3, via electrostatic interaction. These findings offer mechanistic insights into the selective inhibition of TTN3 by NMB\u20101 and provide a foundation for developing therapeutic agents targeting TTN3\u2010related channelopathies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70278","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T13:41:15Z","timestamp":1764510075000},"page":"1845-1859","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular basis for a pore block of Tentonin 3 expressed in HEK293 cells by a conopeptide, NMB\u20101"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8396-809X","authenticated-orcid":false,"given":"Sujin","family":"Lim","sequence":"first","affiliation":[{"name":"Brain Science Institute Korea Institute of Science and Technology (KIST)  Seoul South Korea"},{"name":"Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology Seoul National University  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhyuk","family":"Woo","sequence":"additional","affiliation":[{"name":"Brain Science Institute Korea Institute of Science and Technology (KIST)  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungmin","family":"Pak","sequence":"additional","affiliation":[{"name":"Brain Science Institute Korea Institute of Science and Technology (KIST)  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joonho","family":"Paik","sequence":"additional","affiliation":[{"name":"Brain Science Institute Korea Institute of Science and Technology (KIST)  Seoul South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gyu\u2010Sang","family":"Hong","sequence":"additional","affiliation":[{"name":"Brain Science Institute Korea Institute of Science and 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