{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:56:54Z","timestamp":1788955014924,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"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":["18-74-10088"],"award-info":[{"award-number":["18-74-10088"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Slow-channel congenital myasthenic syndromes (SCCMSs) are rare genetic diseases caused by mutations in muscle nicotinic acetylcholine receptor (nAChR) subunits. Most of the known SCCMS-associated mutations localize at the transmembrane region near the ion pore. Only two SCCMS point mutations are at the extracellular domains near the acetylcholine binding site, \u03b11(G153S) being one of them. In this work, a combination of molecular dynamics, targeted mutagenesis, fluorescent Ca2+ imaging and patch-clamp electrophysiology has been applied to G153S mutant muscle nAChR to investigate the role of hydrogen bonds formed by Ser 153 with C-loop residues near the acetylcholine-binding site. Introduction of L199T mutation to the C-loop in the vicinity of Ser 153 changed hydrogen bonds distribution, decreased acetylcholine potency (EC50 2607 vs. 146 nM) of the double mutant and decay kinetics of acetylcholine-evoked cytoplasmic Ca2+ rise (\u03c4 14.2 \u00b1 0.3 vs. 34.0 \u00b1 0.4 s). These results shed light on molecular mechanisms of nAChR activation-desensitization and on the involvement of such mechanisms in channelopathy genesis.<\/jats:p>","DOI":"10.3390\/molecules26051278","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T09:47:20Z","timestamp":1614332840000},"page":"1278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Point Mutations of Nicotinic Receptor \u03b11 Subunit Reveal New Molecular Features of G153S Slow-Channel Myasthenia"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0313-9193","authenticated-orcid":false,"given":"Denis","family":"Kudryavtsev","sequence":"first","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Isaeva","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"},{"name":"Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Barkova","sequence":"additional","affiliation":[{"name":"Biological Department, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6670-8405","authenticated-orcid":false,"given":"Ekaterina","family":"Spirova","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Mukhutdinova","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"},{"name":"Biological Department, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Kasheverov","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"},{"name":"Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Trubetskaya str. 8, bld. 2, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7980-6191","authenticated-orcid":false,"given":"Victor","family":"Tsetlin","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"},{"name":"Institute of Engineering Physics for Biomedicine, MePhi, 115409 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3389\/fnmol.2020.581097","article-title":"The structure, function, and physiology of the fetal and adult acetylcholine receptor in muscle","volume":"13","author":"Cetin","year":"2020","journal-title":"Front. 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