{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T20:38:15Z","timestamp":1776285495873,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":2081,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T00:00:00Z","timestamp":1496620800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The \u03b13* nAChRs, which are considered to be promising drug targets for problems such as pain, addiction, cardiovascular function, cognitive disorders etc., are found throughout the central and peripheral nervous system. The \u03b1-conotoxin (\u03b1-CTx) LvIA has been identified as the most selective inhibitor of \u03b13\u03b22 nAChRs known to date, and it can distinguish the \u03b13\u03b22 nAChR subtype from the \u03b16\/\u03b13\u03b22\u03b23 and \u03b13\u03b24 nAChR subtypes. However, the mechanism of its selectivity towards \u03b13\u03b22, \u03b16\/\u03b13\u03b22\u03b23, and \u03b13\u03b24 nAChRs remains elusive. Here we report the co-crystal structure of LvIA in complex with Aplysia californica acetylcholine binding protein (Ac-AChBP) at a resolution of 3.4 \u00c5. Based on the structure of this complex, together with homology modeling based on other nAChR subtypes and binding affinity assays, we conclude that Asp-11 of LvIA plays an important role in the selectivity of LvIA towards \u03b13\u03b22 and \u03b13\/\u03b16\u03b22\u03b23 nAChRs by making a salt bridge with Lys-155 of the rat \u03b13 subunit. Asn-9 lies within a hydrophobic pocket that is formed by Met-36, Thr-59, and Phe-119 of the rat \u03b22 subunit in the \u03b13\u03b22 nAChR model, revealing the reason for its more potent selectivity towards the \u03b13\u03b22 nAChR subtype. These results provide molecular insights that can be used to design ligands that selectively target \u03b13\u03b22 nAChRs, with significant implications for the design of new therapeutic \u03b1-CTxs.<\/jats:p>","DOI":"10.1007\/s13238-017-0426-2","type":"journal-article","created":{"date-parts":[[2017,6,4]],"date-time":"2017-06-04T23:29:29Z","timestamp":1496618969000},"page":"675-685","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The crystal structure of Ac-AChBP in complex with \u03b1-conotoxin LvIA reveals the mechanism of its selectivity towards different nAChR subtypes"],"prefix":"10.1093","volume":"8","author":[{"given":"Manyu","family":"Xu","sequence":"first","affiliation":[{"name":"The Ministry of Education Key Laboratory of Protein Science, School of Life Sciences, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Biotherapy, Tsinghua University , 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