{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:01:38Z","timestamp":1787508098322,"version":"build-2736575974"},"reference-count":57,"publisher":"National Academy of Sciences","issue":"6","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["R01NS131299"],"award-info":[{"award-number":["R01NS131299"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,2,10]]},"abstract":"<jats:p>\n                    GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors (GABA\n                    <jats:sub>A<\/jats:sub>\n                    Rs) mediate fast inhibitory neurotransmission in the brain and are assembled from 19 subunit isoforms into multiple pentameric assemblies. Although \u03b11-containing GABA\n                    <jats:sub>A<\/jats:sub>\n                    Rs are broadly expressed and are pharmacologically important, the molecular diversity of native \u03b11-based assemblies in specific brain regions remains incompletely understood. Here, we use immunofluorescence, mass spectrometry, and cryogenic electron microscopy (cryo-EM) to characterize the spatial distribution, subunit composition, and structural architecture of native \u03b11-containing GABA\n                    <jats:sub>A<\/jats:sub>\n                    Rs in the rat cerebellum. Confocal microscopy reveals robust colocalization of \u03b11 and \u03b32 subunits across cerebellar layers, including prominent labeling at glomerular synapses. Biochemical purification and proteomic analysis identify a range of \u03b1, \u03b2, and \u03b3 subunits, along with abundant \u03b16 and \u03b4 subunits. Using cryo-EM and automated subunit identification, we resolve eight \u03b11-containing receptor assemblies, including the first structure of \u03b16-containing receptors. We further determine the binding mode of the \u03b16-selective pyrazoloquinolinone modulator PZ-II-029 at the \u03b1\n                    <jats:sup>+<\/jats:sup>\n                    \/\u03b3\n                    <jats:sup>\u2013<\/jats:sup>\n                    interface, showing ligand-induced expansion of the entire extracellular domain (ECD). Together, our study defines the structure and subunit composition of the \u03b11-containing cerebellar GABA\n                    <jats:sub>A<\/jats:sub>\n                    Rs and elaborates the molecular interactions between native receptors and pyrazoloquinolinone, thereby laying the groundwork for brain region and subunit-specific pharmacology.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2524504123","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T18:48:53Z","timestamp":1770403733000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Molecular assemblies and pharmacology of cerebellar GABA\n                    <sub>A<\/sub>\n                    receptors"],"prefix":"10.1073","volume":"123","author":[{"given":"Chang","family":"Sun","sequence":"first","affiliation":[{"name":"Vollum Institute, Oregon Health and Science University","place":["Portland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer N.","family":"Jahncke","sequence":"additional","affiliation":[{"name":"Vollum Institute, Oregon Health and Science University","place":["Portland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5094-5270","authenticated-orcid":false,"given":"Kevin M.","family":"Wright","sequence":"additional","affiliation":[{"name":"Vollum Institute, Oregon Health and Science University","place":["Portland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8549-2360","authenticated-orcid":false,"given":"Eric","family":"Gouaux","sequence":"additional","affiliation":[{"name":"Vollum Institute, Oregon Health and Science University","place":["Portland"]},{"name":"HHMI, Oregon Health and Science 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