{"entity": "publication", "iuid": "957297ef4b8a432fa5fee3d28bc20905", "timestamp": "2026-08-20T20:42:27.486Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/957297ef4b8a432fa5fee3d28bc20905.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/957297ef4b8a432fa5fee3d28bc20905"}}, "title": "Vestibular modulation by stimulant derivatives in a pentameric ligand-gated ion channel.", "authors": [{"family": "Karlsson", "given": "Emelia", "initials": "E"}, {"family": "And\u00e9n", "given": "Olivia", "initials": "O"}, {"family": "Fan", "given": "Chen", "initials": "C"}, {"family": "Fourati", "given": "Zaineb", "initials": "Z"}, {"family": "Haouz", "given": "Ahmed", "initials": "A"}, {"family": "Zhuang", "given": "Yuxuan", "initials": "Y"}, {"family": "Howard", "given": "Rebecca J", "initials": "RJ", "orcid": "0000-0003-2049-3378", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ce04593b5b24aaa8978fda1447dd0bf.json"}}, {"family": "Delarue", "given": "Marc", "initials": "M"}, {"family": "Lindahl", "given": "Erik", "initials": "E"}], "type": "journal article", "published": "2025-06-00", "journal": {"title": "Br J Pharmacol", "issn": "1476-5381", "volume": "182", "issue": "12", "pages": "2790-2802", "issn-l": null}, "abstract": "Allosteric modulation of pentameric ligand-gated ion channels (pLGICs) are critical for the action of neurotransmitters and many psychoactive drugs. However, details of their modulatory mechanisms remain unclear, especially beyond the orthosteric neurotransmitter-binding sites. The recently reported prokaryotic symbiont of Tevnia jerichonana ligand-gated ion channel (sTeLIC), a pH-gated homologue of eukaryotic receptors in the pLGIC family, is thought to be modulated by aromatic compounds via a relatively uncharacterised modulatory site in the extracellular vestibule.\n\nWe have characterised the effects of psychostimulant derivatives on sTeLIC using two-electrode voltage-clamp electrophysiology in the presence and absence of engineered mutations, and determined X-ray and cryo-EM structures of the channel in both closed and open states.\n\nWe have shown that sTeLIC is sensitive to potentiation by several amphiphilic compounds, which preferentially bind to a vestibular pocket in the contracted open-state extracellular domain.\n\nThis work provides a detailed structure-function mechanism for allosteric potentiation via a noncanonical ligand site, with potential conservation of the eukaryotic pentameric ligand-gated ion channels.", "doi": "10.1111/bph.70011", "pmid": "40065647", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:17:27.756Z", "modified": "2026-08-20T11:17:27.822Z"}