{"entity": "publication", "iuid": "2c65a482ba864441852de1f61b7ac256", "timestamp": "2026-08-20T20:36:34.900Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2c65a482ba864441852de1f61b7ac256.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2c65a482ba864441852de1f61b7ac256"}}, "title": "Cryo-EM structures of \u03c11 GABAA receptors with antagonist and agonist drugs.", "authors": [{"family": "Fan", "given": "Chen", "initials": "C", "orcid": "0000-0003-1211-3427", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8690704777ea45e992b25523219e8b56.json"}}, {"family": "Cowgill", "given": "John", "initials": "J", "orcid": "0000-0002-7968-8359", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/861488d03cd8493388b75eab8476381d.json"}}, {"family": "Howard", "given": "Rebecca J", "initials": "RJ", "orcid": "0000-0003-2049-3378", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ce04593b5b24aaa8978fda1447dd0bf.json"}}, {"family": "Lindahl", "given": "Erik", "initials": "E", "orcid": "0000-0002-2734-2794", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9eb30fa60f9b4b95842ac9d9f3a0eaa9.json"}}], "type": "journal article", "published": "2025-08-01", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "7077", "issn-l": "2041-1723"}, "abstract": "The family of \u03c1-type GABAA receptors includes potential therapeutic targets in several neurological conditions, and features distinctive pharmacology compared to other subtypes. Here we report four cryo-EM structures with previously unresolved ligands, electrophysiology recordings, and molecular dynamics simulations to characterize binding and conformational impact of the drugs THIP (a non-opioid analgesic), CGP36742 (a phosphinic acid) and GABOB (an anticonvulsant) on a human \u03c11 GABAA receptor. A distinctive binding pose of THIP in \u03c11 versus \u03b14\u03b23\u03b4 GABAA receptors offers a rationale for its inverse effects on these subtypes. CGP36742 binding is similar to the canonical \u03c1-type inhibitor TPMPA, supporting a shared mechanism of action among phosphinic acids. Binding of GABOB is similar to GABA, but produces a mixture of partially-locked and desensitized states, likely underlying weaker agonist activity. Together, these results elucidate interactions of a \u03c1-type GABAA receptor with therapeutic drugs, offering mechanistic insights and a basis for further pharmaceutical development.", "doi": "10.1038/s41467-025-61932-6", "pmid": "40750757", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12316911"}, {"db": "pii", "key": "10.1038/s41467-025-61932-6"}], "notes": [], "created": "2026-08-20T08:53:59.682Z", "modified": "2026-08-20T08:53:59.770Z"}