{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:46:31Z","timestamp":1789908391462,"version":"4.0.1"},"reference-count":54,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,12,13]],"date-time":"2018-12-13T00:00:00Z","timestamp":1544659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81660585"],"award-info":[{"award-number":["81660585"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31760249"],"award-info":[{"award-number":["31760249"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Major International Joint Research Project of National Natural Science Foundation of China","award":["81420108028"],"award-info":[{"award-number":["81420108028"]}]},{"name":"Hainan University Youth foundation","award":["hdkyx201725"],"award-info":[{"award-number":["hdkyx201725"]}]},{"name":"Changjiang Scholars and Innovative Research Team in University Grant","award":["IRT_15R15"],"award-info":[{"award-number":["IRT_15R15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Recently, the muscle-type nicotinic acetylcholine receptors (nAChRs) have been pursued as a potential target of several diseases, including myogenic disorders, muscle dystrophies and myasthenia gravis, etc. \u03b1-conotoxin GI isolated from Conus geographus selectively and potently inhibited the muscle-type nAChRs which can be developed as a tool to study them. Herein, alanine scanning mutagenesis was used to reveal the structure\u2013activity relationship (SAR) between GI and mouse \u03b11\u03b21\u03b4\u03b5 nAChRs. The Pro5, Gly8, Arg9, and Tyr11 were proved to be the critical residues for receptor inhibiting as the alanine (Ala) replacement led to a significant potency loss on mouse \u03b11\u03b21\u03b4\u03b5 nAChR. On the contrary, substituting Asn4, His10 and Ser12 with Ala respectively did not affect its activity. Interestingly, the [E1A] GI analogue exhibited a three-fold potency for mouse \u03b11\u03b21\u03b4\u03b5 nAChR, whereas it obviously decreased potency at rat \u03b19\u03b110 nAChR compared to wildtype GI. Molecular dynamic simulations also suggest that loop2 of GI significantly affects the interaction with \u03b11\u03b21\u03b4\u03b5 nAChR, and Tyr11 of GI is a critical residue binding with three hydrophobic amino acids of the \u03b4 subunit, including Leu93, Tyr95 and Leu103. Our research elucidates the interaction of GI and mouse \u03b11\u03b21\u03b4\u03b5 nAChR in detail that will help to develop the novel analogues of GI.<\/jats:p>","DOI":"10.3390\/md16120507","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T03:58:17Z","timestamp":1544759897000},"page":"507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Alanine-Scanning Mutagenesis of \u03b1-Conotoxin GI Reveals the Residues Crucial for Activity at the Muscle Acetylcholine Receptor"],"prefix":"10.3390","volume":"16","author":[{"given":"Jiong","family":"Ning","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou 570228, Hainan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou 570228, Hainan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ren","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou 570228, Hainan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongting","family":"Zhangsun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou 570228, Hainan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou 570228, Hainan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou 570228, Hainan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-5970","authenticated-orcid":false,"given":"Sulan","family":"Luo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources, Ministry of Education, Key Lab for Marine Drugs of Haikou, Hainan University, Haikou 570228, Hainan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.pharmthera.2012.08.012","article-title":"Nicotinic acetylcholine receptors: From basic science to therapeutics","volume":"137","author":"Hurst","year":"2013","journal-title":"Pharmacol. 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