{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T14:33:50Z","timestamp":1791124430361,"version":"4.1.0"},"reference-count":73,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T00:00:00Z","timestamp":1532476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T00:00:00Z","timestamp":1532476800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T00:00:00Z","timestamp":1532476800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01 GM100400"],"award-info":[{"award-number":["R01 GM100400"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases. Despite the profound importance of heteromeric GABAA receptors in neuroscience and medicine, they have proven recalcitrant to structure determination. Here we present the structure of a tri-heteromeric \u03b11\u03b21\u03b32SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1\u20133.8 \u00c5 resolution, elucidating molecular principles of receptor assembly and agonist binding. Remarkable N-linked glycosylation on the \u03b11 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating. Our work provides a pathway to structural studies of heteromeric GABAA receptors and a framework for rational design of novel therapeutic agents.<\/jats:p>","DOI":"10.7554\/elife.39383","type":"journal-article","created":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T08:00:19Z","timestamp":1532505619000},"source":"Crossref","is-referenced-by-count":166,"title":["Cryo-EM structure of the benzodiazepine-sensitive \u03b11\u03b21\u03b32S tri-heteromeric GABAA receptor in complex with GABA"],"prefix":"10.7554","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1272-7712","authenticated-orcid":true,"given":"Swastik","family":"Phulera","sequence":"first","affiliation":[{"name":"Vollum Institute, Oregon Health and Science University, Portland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1522-0500","authenticated-orcid":true,"given":"Hongtao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Vollum 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