{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:57:39Z","timestamp":1788299859274,"version":"build-2803163510"},"reference-count":84,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-14-00326"],"award-info":[{"award-number":["22-14-00326"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>TRPA1 is a homotetrameric non-selective calcium-permeable channel. It contributes to chemical and temperature sensitivity, acute pain sensation, and development of inflammation. HCIQ2c1 is a peptide from the sea anemone Heteractis magnifica that inhibits serine proteases. Here, we showed that HCIQ2c1 significantly reduces AITC- and capsaicin-induced pain and inflammation in mice. Electrophysiology recordings in Xenopus oocytes expressing rat TRPA1 channel revealed that HCIQ2c1 binds to open TRPA1 and prevents its transition to closed and inhibitor-insensitive \u2018hyperactivated\u2019 states. NMR study of the 15N-labeled recombinant HCIQ2c1 analog described a classical Kunitz-type structure and revealed two dynamic hot-spots (loops responsible for protease binding and regions near the N- and C-termini) that exhibit simultaneous mobility on two timescales (ps\u2013ns and \u03bcs\u2013ms). In modelled HCIQ2c1\/TRPA1 complex, the peptide interacts simultaneously with one voltage-sensing-like domain and two pore domain fragments from different channel\u2019s subunits, and with lipid molecules. The model explains stabilization of the channel in the open conformation and the restriction of \u2018hyperactivation\u2019, which are probably responsible for the observed analgetic activity. HCIQ2c1 is the third peptide ligand of TRPA1 from sea anemones and the first Kunitz-type ligand of this channel. HCIQ2c1 is a prototype of efficient analgesic and anti-inflammatory drugs.<\/jats:p>","DOI":"10.3390\/md22120542","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T04:04:04Z","timestamp":1733198644000},"page":"542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sea Anemone Kunitz Peptide HCIQ2c1: Structure, Modulation of TRPA1 Channel, and Suppression of Nociceptive Reaction In Vivo"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0937-002X","authenticated-orcid":false,"given":"Aleksandra N.","family":"Kvetkina","sequence":"first","affiliation":[{"name":"G.B. 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Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7212-1360","authenticated-orcid":false,"given":"Dmitrii S.","family":"Kulbatskii","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia A.","family":"Logashina","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7628-0980","authenticated-orcid":false,"given":"Yaroslav A.","family":"Andreev","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1331-3949","authenticated-orcid":false,"given":"Anton O.","family":"Chugunov","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, 123592 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail P.","family":"Kirpichnikov","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia"},{"name":"Interdisciplinary Scientific and Educational School of Moscow University \u00abMolecular Technologies of the Living Systems and Synthetic Biology\u00bb, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9728-9407","authenticated-orcid":false,"given":"Ekaterina N.","family":"Lyukmanova","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, 123592 Moscow, Russia"},{"name":"Interdisciplinary Scientific and Educational School of Moscow University \u00abMolecular Technologies of the Living Systems and Synthetic Biology\u00bb, Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia"},{"name":"Shenzhen MSU-BIT University, No. 1, International University Park Road, Dayun New Town, Longgang District, Shenzhen 518172, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2360-1365","authenticated-orcid":false,"given":"Elena V.","family":"Leychenko","sequence":"additional","affiliation":[{"name":"G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, Russia"},{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1383-3522","authenticated-orcid":false,"given":"Zakhar O.","family":"Shenkarev","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, 123592 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41392-023-01464-x","article-title":"TRP (Transient Receptor Potential) Ion Channel Family: Structures, Biological Functions and Therapeutic Interventions for Diseases","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. 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