{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:16:06Z","timestamp":1794003366392,"version":"4.8.0"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"7904","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2022,4,7]]},"DOI":"10.1038\/s41586-022-04517-3","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T12:39:06Z","timestamp":1648643946000},"page":"190-194","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":121,"title":["Differential assembly diversifies GABAA receptor structures and signalling"],"prefix":"10.1038","volume":"604","author":[{"given":"Andrija","family":"Sente","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rooma","family":"Desai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Naydenova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4847-5529","authenticated-orcid":false,"given":"Tomas","family":"Malinauskas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssef","family":"Jounaidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Miehling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simonas","family":"Masiulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9246-1864","authenticated-orcid":false,"given":"Steven W.","family":"Hardwick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9942-0993","authenticated-orcid":false,"given":"Dimitri Y.","family":"Chirgadze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4105-6639","authenticated-orcid":false,"given":"Keith W.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3783-1388","authenticated-orcid":false,"given":"A. Radu","family":"Aricescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"4517_CR1","doi-asserted-by":"publisher","first-page":"40224","DOI":"10.1074\/jbc.R112.386664","volume":"287","author":"E Sigel","year":"2012","unstructured":"Sigel, E. & Steinmann, M. E. Structure, function, and modulation of GABAA receptors. J. Biol. Chem. 287, 40224\u201340231 (2012).","journal-title":"J. Biol. Chem."},{"key":"4517_CR2","doi-asserted-by":"publisher","first-page":"795","DOI":"10.2174\/1568026023393507","volume":"2","author":"W Sieghart","year":"2002","unstructured":"Sieghart, W. & Sperk, G. Subunit composition, distribution and function of GABAA receptor subtypes. Curr. Top. Med. Chem. 2, 795\u2013816 (2002).","journal-title":"Curr. Top. Med. Chem."},{"key":"4517_CR3","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1124\/pr.117.014449","volume":"70","author":"W Sieghart","year":"2018","unstructured":"Sieghart, W. & Savic, M. M. International Union of Basic and Clinical Pharmacology. CVI: GABAA receptor subtype- and function-selective ligands: key issues in translation to humans. Pharmacol. Rev. 70, 836\u2013878 (2018).","journal-title":"Pharmacol. Rev."},{"key":"4517_CR4","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41586-018-0255-3","volume":"559","author":"S Zhu","year":"2018","unstructured":"Zhu, S. et al. Structure of a human synaptic GABAA receptor. Nature 559, 67\u201372 (2018).","journal-title":"Nature"},{"key":"4517_CR5","doi-asserted-by":"publisher","first-page":"e39383","DOI":"10.7554\/eLife.39383","volume":"7","author":"S Phulera","year":"2018","unstructured":"Phulera, S. et al. Cryo-EM structure of the benzodiazepine-sensitive \u03b11\u03b21\u03b32S tri-heteromeric GABAA receptor in complex with GABA. eLife 7, e39383 (2018).","journal-title":"eLife"},{"key":"4517_CR6","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1038\/s41586-018-0833-4","volume":"565","author":"D Laverty","year":"2019","unstructured":"Laverty, D. et al. Cryo-EM structure of the human \u03b11\u03b23\u03b32 GABAA receptor in a lipid bilayer. Nature 565, 516\u2013520 (2019).","journal-title":"Nature"},{"key":"4517_CR7","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1038\/s41586-018-0832-5","volume":"565","author":"S Masiulis","year":"2019","unstructured":"Masiulis, S. et al. GABAA receptor signalling mechanisms revealed by structural pharmacology. Nature 565, 454\u2013459 (2019).","journal-title":"Nature"},{"key":"4517_CR8","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41586-018-0654-5","volume":"563","author":"B Tasic","year":"2018","unstructured":"Tasic, B. et al. Shared and distinct transcriptomic cell types across neocortical areas. Nature 563, 72\u201378 (2018).","journal-title":"Nature"},{"key":"4517_CR9","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/s41586-019-1506-7","volume":"573","author":"RD Hodge","year":"2019","unstructured":"Hodge, R. D. et al. Conserved cell types with divergent features in human versus mouse cortex. Nature 573, 61\u201368 (2019).","journal-title":"Nature"},{"key":"4517_CR10","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1523\/JNEUROSCI.12-03-01040.1992","volume":"12","author":"W Wisden","year":"1992","unstructured":"Wisden, W., Laurie, D. J., Monyer, H. & Seeburg, P. H. The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. J. Neurosci. 12, 1040\u20131062 (1992).","journal-title":"J. Neurosci."},{"key":"4517_CR11","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1523\/JNEUROSCI.18-05-01693.1998","volume":"18","author":"Z Nusser","year":"1998","unstructured":"Nusser, Z., Sieghart, W. & Somogyi, P. Segregation of different GABAA receptors to synaptic and extrasynaptic membranes of cerebellar granule cells. J. Neurosci. 18, 1693\u20131703 (1998).","journal-title":"J. Neurosci."},{"key":"4517_CR12","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0896-6273(93)90310-N","volume":"10","author":"RA Pearce","year":"1993","unstructured":"Pearce, R. A. Physiological evidence for two distinct GABAA responses in rat hippocampus. Neuron 10, 189\u2013200 (1993).","journal-title":"Neuron"},{"key":"4517_CR13","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/0306-4522(92)90513-2","volume":"51","author":"A Baude","year":"1992","unstructured":"Baude, A., Sequier, J. M., McKernan, R. M., Olivier, K. R. & Somogyi, P. Differential subcellular distribution of the alpha 6 subunit versus the alpha 1 and beta 2\/3 subunits of the GABAA\/benzodiazepine receptor complex in granule cells of the cerebellar cortex. Neuroscience 51, 739\u2013748 (1992).","journal-title":"Neuroscience"},{"key":"4517_CR14","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/nrn1625","volume":"6","author":"M Farrant","year":"2005","unstructured":"Farrant, M. & Nusser, Z. Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors. Nat. Rev. Neurosci. 6, 215\u2013229 (2005).","journal-title":"Nat. Rev. Neurosci."},{"key":"4517_CR15","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.neuron.2011.12.012","volume":"73","author":"SG Brickley","year":"2012","unstructured":"Brickley, S. G. & Mody, I. Extrasynaptic GABAA receptors: their function in the CNS and implications for disease. Neuron 73, 23\u201334 (2012).","journal-title":"Neuron"},{"key":"4517_CR16","doi-asserted-by":"publisher","first-page":"591129","DOI":"10.3389\/fnsyn.2020.591129","volume":"12","author":"P Scholze","year":"2020","unstructured":"Scholze, P. et al. Two distinct populations of \u03b11\u03b16-containing GABAA-receptors in rat cerebellum. Front. Synaptic Neurosci. 12, 591129 (2020).","journal-title":"Front. Synaptic Neurosci."},{"key":"4517_CR17","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1124\/mol.107.042481","volume":"73","author":"NP Barrera","year":"2008","unstructured":"Barrera, N. P. et al. Atomic force microscopy reveals the stoichiometry and subunit arrangement of the \u03b14\u03b23\u03b4 GABAA receptor. Mol. Pharmacol. 73, 960\u2013967 (2008).","journal-title":"Mol. Pharmacol."},{"key":"4517_CR18","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1111\/bph.12514","volume":"171","author":"B Patel","year":"2014","unstructured":"Patel, B., Mortensen, M. & Smart, T. G. Stoichiometry of delta subunit containing GABAA receptors. Br. J. Pharmacol. 171, 985\u2013994 (2014).","journal-title":"Br. J. Pharmacol."},{"key":"4517_CR19","doi-asserted-by":"publisher","first-page":"14187","DOI":"10.1074\/jbc.M110.104257","volume":"285","author":"KR Wagoner","year":"2010","unstructured":"Wagoner, K. R. & Czajkowski, C. Stoichiometry of expressed \u03b14\u03b22\u03b4 \u03b3-aminobutyric acid type A receptors depends on the ratio of subunit cDNA transfected. J. Biol. Chem. 285, 14187\u201314194 (2010).","journal-title":"J. Biol. Chem."},{"key":"4517_CR20","doi-asserted-by":"publisher","first-page":"20440","DOI":"10.1074\/jbc.M115.698860","volume":"291","author":"EJ Botzolakis","year":"2016","unstructured":"Botzolakis, E. J. et al. Comparison of gamma-aminobutyric acid, type A (GABAA), receptor \u03b1\u03b2\u03b3 and \u03b1\u03b2\u03b4 expression using flow cytometry and electrophysiology: evidence for alternative subunit stoichiometries and arrangements. J. Biol. Chem. 291, 20440\u201320461 (2016).","journal-title":"J. Biol. Chem."},{"key":"4517_CR21","doi-asserted-by":"publisher","first-page":"e0191583","DOI":"10.1371\/journal.pone.0191583","volume":"13","author":"X Zhou","year":"2018","unstructured":"Zhou, X. et al. High-level production and purification in a functional state of an extrasynaptic gamma-aminobutyric acid type A receptor containing \u03b14\u03b23\u03b4 subunits. PLoS ONE 13, e0191583 (2018).","journal-title":"PLoS ONE"},{"key":"4517_CR22","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1124\/mol.114.094813","volume":"86","author":"MM Eaton","year":"2014","unstructured":"Eaton, M. M. et al. \u03b3-Aminobutyric acid type A \u03b14, \u03b22, and \u03b4 subunits assemble to produce more than one functionally distinct receptor type. Mol. Pharmacol. 86, 647\u2013656 (2014).","journal-title":"Mol. Pharmacol."},{"key":"4517_CR23","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/s41586-020-2829-0","volume":"587","author":"T Nakane","year":"2020","unstructured":"Nakane, T. et al. Single-particle cryo-EM at atomic resolution. Nature 587, 152\u2013156 (2020).","journal-title":"Nature"},{"key":"4517_CR24","doi-asserted-by":"publisher","first-page":"10470","DOI":"10.1074\/jbc.M709993200","volume":"283","author":"A Saras","year":"2008","unstructured":"Saras, A. et al. Histamine action on vertebrate GABAA receptors: direct channel gating and potentiation of GABA responses. J. Biol. Chem. 283, 10470\u201310475 (2008).","journal-title":"J. Biol. Chem."},{"key":"4517_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15628-7","volume":"7","author":"N Wongsamitkul","year":"2017","unstructured":"Wongsamitkul, N. et al. \u03b1 Subunits in GABAA receptors are dispensable for GABA and diazepam action. Sci. Rep. 7, 15498 (2017).","journal-title":"Sci. Rep."},{"key":"4517_CR26","doi-asserted-by":"publisher","first-page":"6360","DOI":"10.1523\/JNEUROSCI.19-15-06360.1999","volume":"19","author":"PM Taylor","year":"1999","unstructured":"Taylor, P. M. et al. Identification of amino acid residues within GABAA receptor beta subunits that mediate both homomeric and heteromeric receptor expression. J. Neurosci. 19, 6360\u20136371 (1999).","journal-title":"J. Neurosci."},{"key":"4517_CR27","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/j.neuropharm.2011.05.020","volume":"61","author":"MT Bianchi","year":"2011","unstructured":"Bianchi, M. T., Clark, A. G. & Fisher, J. L. The wake-promoting transmitter histamine preferentially enhances alpha-4 subunit-containing GABAA receptors. Neuropharmacology 61, 747\u2013752 (2011).","journal-title":"Neuropharmacology"},{"key":"4517_CR28","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.brainres.2016.05.019","volume":"1644","author":"HJ Lee","year":"2016","unstructured":"Lee, H. J. et al. A pharmacological characterization of GABA, THIP and DS2 at binary \u03b14\u03b23 and \u03b23\u03b4 receptors: GABA activates \u03b23\u03b4 receptors via the \u03b23+\u03b4\u2212 interface. Brain Res. 1644, 222\u2013230 (2016).","journal-title":"Brain Res."},{"key":"4517_CR29","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/nature13293","volume":"512","author":"PS Miller","year":"2014","unstructured":"Miller, P. S. & Aricescu, A. R. Crystal structure of a human GABAA receptor. Nature 512, 270\u2013275 (2014).","journal-title":"Nature"},{"key":"4517_CR30","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.neuropharm.2016.04.042","volume":"108","author":"P Hoerbelt","year":"2016","unstructured":"Hoerbelt, P. et al. Mutagenesis and computational docking studies support the existence of a histamine binding site at the extracellular \u03b23+ \u03b23\u2212 interface of homooligomeric \u03b23 GABAA receptors. Neuropharmacology 108, 252\u2013263 (2016).","journal-title":"Neuropharmacology"},{"key":"4517_CR31","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1111\/j.1471-4159.1982.tb05357.x","volume":"38","author":"E Falch","year":"1982","unstructured":"Falch, E. & Krogsgaard-Larsen, P. The binding of the GABA agonist [3H]THIP to rat brain synaptic membranes. J. Neurochem. 38, 1123\u20131129 (1982).","journal-title":"J. Neurochem."},{"key":"4517_CR32","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.coph.2005.10.004","volume":"6","author":"KA Wafford","year":"2006","unstructured":"Wafford, K. A. & Ebert, B. Gaboxadol\u2014a new awakening in sleep. Curr. Opin. Pharmacol. 6, 30\u201336 (2006).","journal-title":"Curr. Opin. Pharmacol."},{"key":"4517_CR33","doi-asserted-by":"publisher","first-page":"8546","DOI":"10.1073\/pnas.0509903103","volume":"103","author":"HJ Hanchar","year":"2006","unstructured":"Hanchar, H. J. et al. Ethanol potently and competitively inhibits binding of the alcohol antagonist Ro15-4513 to \u03b14\/6\u03b23\u03b4 GABAA receptors. Proc. Natl Acad. Sci. USA 103, 8546\u20138551 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4517_CR34","doi-asserted-by":"publisher","first-page":"8540","DOI":"10.1073\/pnas.0600194103","volume":"103","author":"M Wallner","year":"2006","unstructured":"Wallner, M., Hanchar, H. J. & Olsen, R. W. Low-dose alcohol actions on \u03b14\u03b23\u03b4 GABAA receptors are reversed by the behavioral alcohol antagonist Ro15-4513. Proc. Natl Acad. Sci. USA 103, 8540\u20138545 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4517_CR35","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.alcohol.2007.04.006","volume":"41","author":"RW Olsen","year":"2007","unstructured":"Olsen, R. W., Hanchar, H. J., Meera, P. & Wallner, M. GABAA receptor subtypes: the \u201cone glass of wine\u201d receptors. Alcohol 41, 201\u2013209 (2007).","journal-title":"Alcohol"},{"key":"4517_CR36","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3389\/fnins.2011.00003","volume":"5","author":"AM Linden","year":"2011","unstructured":"Linden, A. M. et al. Ro 15-4513 antagonizes alcohol-induced sedation in mice through \u03b1\u03b2\u03b32-type GABAA receptors. Front. Neurosci. 5, 3 (2011).","journal-title":"Front. Neurosci."},{"key":"4517_CR37","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1124\/jpet.105.092403","volume":"316","author":"SI Storustovu","year":"2006","unstructured":"Storustovu, S. I. & Ebert, B. Pharmacological characterization of agonists at delta-containing GABAA receptors: functional selectivity for extrasynaptic receptors is dependent on the absence of \u03b32. J. Pharmacol. Exp. Ther. 316, 1351\u20131359 (2006).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"4517_CR38","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1038\/sj.bjp.0704795","volume":"136","author":"N Brown","year":"2002","unstructured":"Brown, N., Kerby, J., Bonnert, T. P., Whiting, P. J. & Wafford, K. A. Pharmacological characterization of a novel cell line expressing human \u03b14\u03b23\u03b4 GABAA receptors. Br. J. Pharmacol. 136, 965\u2013974 (2002).","journal-title":"Br. J. Pharmacol."},{"key":"4517_CR39","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/s41586-020-2888-2","volume":"587","author":"M Marti-Solano","year":"2020","unstructured":"Marti-Solano, M. et al. Combinatorial expression of GPCR isoforms affects signalling and drug responses. Nature 587, 650\u2013656 (2020).","journal-title":"Nature"},{"key":"4517_CR40","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/nrd3502","volume":"10","author":"U Rudolph","year":"2011","unstructured":"Rudolph, U. & Knoflach, F. Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes. Nat. Rev. Drug Discov. 10, 685\u2013697 (2011).","journal-title":"Nat. Rev. Drug Discov."},{"key":"4517_CR41","doi-asserted-by":"publisher","first-page":"19613","DOI":"10.1074\/jbc.274.28.19613","volume":"274","author":"E Bencsits","year":"1999","unstructured":"Bencsits, E., Ebert, V., Tretter, V. & Sieghart, W. A significant part of native \u03b3-aminobutyric acidA receptors containing \u03b14 subunits do not contain \u03b3 or \u03b4 subunits. J. Biol. Chem. 274, 19613\u201319616 (1999).","journal-title":"J. Biol. Chem."},{"key":"4517_CR42","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/335076a0","volume":"335","author":"ES Levitan","year":"1988","unstructured":"Levitan, E. S. et al. Structural and functional basis for GABAA receptor heterogeneity. Nature 335, 76\u201379 (1988).","journal-title":"Nature"},{"key":"4517_CR43","doi-asserted-by":"publisher","first-page":"2960","DOI":"10.1523\/JNEUROSCI.19-08-02960.1999","volume":"19","author":"SG Brickley","year":"1999","unstructured":"Brickley, S. G., Cull-Candy, S. G. & Farrant, M. Single-channel properties of synaptic and extrasynaptic GABAA receptors suggest differential targeting of receptor subtypes. J. Neurosci. 19, 2960\u20132973 (1999).","journal-title":"J. Neurosci."},{"key":"4517_CR44","doi-asserted-by":"publisher","first-page":"5965","DOI":"10.1016\/S0021-9258(18)53413-X","volume":"268","author":"S Mertens","year":"1993","unstructured":"Mertens, S., Benke, D. & Mohler, H. GABAA receptor populations with novel subunit combinations and drug binding profiles identified in brain by \u03b15- and \u03b4-subunit-specific immunopurification. J. Biol. Chem. 268, 5965\u20135973 (1993).","journal-title":"J. Biol. Chem."},{"key":"4517_CR45","doi-asserted-by":"publisher","first-page":"6726","DOI":"10.1073\/pnas.89.15.6726","volume":"89","author":"JM Fritschy","year":"1992","unstructured":"Fritschy, J. M. et al. Five subtypes of type A gamma-aminobutyric acid receptors identified in neurons by double and triple immunofluorescence staining with subunit-specific antibodies. Proc. Natl Acad. Sci. USA 89, 6726\u20136730 (1992).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4517_CR46","doi-asserted-by":"publisher","first-page":"24778","DOI":"10.1016\/S0021-9258(18)54297-6","volume":"266","author":"MJ Duggan","year":"1991","unstructured":"Duggan, M. J., Pollard, S. & Stephenson, F. A. Immunoaffinity purification of GABAA receptor \u03b1-subunit iso-oligomers. Demonstration of receptor populations containing \u03b11 \u03b12, \u03b11 \u03b13, and \u03b12 \u03b13 subunit pairs. J. Biol. Chem. 266, 24778\u201324784 (1991).","journal-title":"J. Biol. Chem."},{"key":"4517_CR47","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/nrn919","volume":"3","author":"DF Owens","year":"2002","unstructured":"Owens, D. F. & Kriegstein, A. R. Is there more to GABA than synaptic inhibition? Nat. Rev. Neurosci. 3, 715\u2013727 (2002).","journal-title":"Nat. Rev. Neurosci."},{"key":"4517_CR48","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1093\/cercor\/bhu040","volume":"25","author":"D Datta","year":"2015","unstructured":"Datta, D., Arion, D. & Lewis, D. A. Developmental expression patterns of GABAA receptor subunits in layer 3 and 5 pyramidal cells of monkey prefrontal cortex. Cereb. Cortex 25, 2295\u20132305 (2015).","journal-title":"Cereb. Cortex"},{"key":"4517_CR49","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2013.64","volume":"3","author":"SH Fatemi","year":"2013","unstructured":"Fatemi, S. H., Folsom, T. D., Rooney, R. J. & Thuras, P. D. Expression of GABAA \u03b12-, \u03b21- and \u03b5-receptors are altered significantly in the lateral cerebellum of subjects with schizophrenia, major depression and bipolar disorder. Transl. Psychiatry 3, e303 (2013).","journal-title":"Transl. Psychiatry"},{"key":"4517_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2015.102","volume":"5","author":"TM Mueller","year":"2015","unstructured":"Mueller, T. M., Remedies, C. E., Haroutunian, V. & Meador-Woodruff, J. H. Abnormal subcellular localization of GABAA receptor subunits in schizophrenia brain. Transl. Psychiatry 5, e612 (2015).","journal-title":"Transl. Psychiatry"},{"key":"4517_CR51","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1107\/S0907444911001314","volume":"67","author":"GN Murshudov","year":"2011","unstructured":"Murshudov, G. N. et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D Biol. Crystallogr. 67, 355\u2013367 (2011).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"4517_CR52","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1107\/S0907444909042073","volume":"66","author":"VB Chen","year":"2010","unstructured":"Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 12\u201321 (2010).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"4517_CR53","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1107\/S2059798318006551","volume":"74","author":"PV Afonine","year":"2018","unstructured":"Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D Struct. Biol. 74, 531\u2013544 (2018).","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"4517_CR54","doi-asserted-by":"publisher","first-page":"13413","DOI":"10.1073\/pnas.212519199","volume":"99","author":"PJ Reeves","year":"2002","unstructured":"Reeves, P. J., Kim, J. M. & Khorana, H. G. Structure and function in rhodopsin: a tetracycline-inducible system in stable mammalian cell lines for high-level expression of opsin mutants. Proc. Natl Acad. Sci. USA 99, 13413\u201313418 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4517_CR55","doi-asserted-by":"publisher","first-page":"2991","DOI":"10.1038\/s41596-018-0075-9","volume":"13","author":"J Elegheert","year":"2018","unstructured":"Elegheert, J. et al. Lentiviral transduction of mammalian cells for fast, scalable and high-level production of soluble and membrane proteins. Nat. Protoc. 13, 2991\u20133017 (2018).","journal-title":"Nat. Protoc."},{"key":"4517_CR56","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1002\/pro.2401","volume":"23","author":"Z Dostalova","year":"2014","unstructured":"Dostalova, Z. et al. Human \u03b11\u03b23\u03b32L \u03b3-aminobutyric acid type A receptors: high-level production and purification in a functional state. Protein Sci. 23, 157\u2013166 (2014).","journal-title":"Protein Sci."},{"key":"4517_CR57","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/nsmb.3484","volume":"24","author":"PS Miller","year":"2017","unstructured":"Miller, P. S. et al. Structural basis for GABAA receptor potentiation by neurosteroids. Nat. Struct. Mol. Biol. 24, 986\u2013992 (2017).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"4517_CR58","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/s41592-020-01001-6","volume":"18","author":"T Uchanski","year":"2021","unstructured":"Uchanski, T. et al. Megabodies expand the nanobody toolkit for protein structure determination by single-particle cryo-EM. Nat. Methods 18, 60\u201368 (2021).","journal-title":"Nat. Methods"},{"key":"4517_CR59","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1126\/science.1259530","volume":"346","author":"CJ Russo","year":"2014","unstructured":"Russo, C. J. & Passmore, L. A. Electron microscopy: ultrastable gold substrates for electron cryomicroscopy. Science 346, 1377\u20131380 (2014).","journal-title":"Science"},{"key":"4517_CR60","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nmeth.4193","volume":"14","author":"SQ Zheng","year":"2017","unstructured":"Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331\u2013332 (2017).","journal-title":"Nat. Methods"},{"key":"4517_CR61","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.jsb.2015.08.008","volume":"192","author":"A Rohou","year":"2015","unstructured":"Rohou, A. & Grigorieff, N. CTFFIND4: fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216\u2013221 (2015).","journal-title":"J. Struct. Biol."},{"key":"4517_CR62","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1038\/s41592-019-0580-y","volume":"16","author":"D Tegunov","year":"2019","unstructured":"Tegunov, D. & Cramer, P. Real-time cryo-electron microscopy data preprocessing with Warp. Nat. Methods 16, 1146\u20131152 (2019).","journal-title":"Nat. Methods"},{"key":"4517_CR63","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nmeth.4169","volume":"14","author":"A Punjani","year":"2017","unstructured":"Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290\u2013296 (2017).","journal-title":"Nat. Methods"},{"key":"4517_CR64","unstructured":"Asarnow, D., Palovcak, E. & Cheng, Y. asarnow\/pyem: UCSF pyem v0.5 (Zenodo, 2019)."},{"key":"4517_CR65","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.jsb.2012.09.006","volume":"180","author":"SH Scheres","year":"2012","unstructured":"Scheres, S. H. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519\u2013530 (2012).","journal-title":"J. Struct. Biol."},{"key":"4517_CR66","doi-asserted-by":"publisher","first-page":"e42166","DOI":"10.7554\/eLife.42166","volume":"7","author":"J Zivanov","year":"2018","unstructured":"Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).","journal-title":"eLife"},{"key":"4517_CR67","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1107\/S2052252520000081","volume":"7","author":"J Zivanov","year":"2020","unstructured":"Zivanov, J., Nakane, T. & Scheres, S. H. W. Estimation of high-order aberrations and anisotropic magnification from cryo-EM data sets in RELION-3.1. IUCrJ 7, 253\u2013267 (2020).","journal-title":"IUCrJ"},{"key":"4517_CR68","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1107\/S205225251801463X","volume":"6","author":"J Zivanov","year":"2019","unstructured":"Zivanov, J., Nakane, T. & Scheres, S. H. W. A Bayesian approach to beam-induced motion correction in cryo-EM single-particle analysis. IUCrJ 6, 5\u201317 (2019).","journal-title":"IUCrJ"},{"key":"4517_CR69","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen, E. F. et al. UCSF Chimera\u2014a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605\u20131612 (2004).","journal-title":"J. Comput. Chem."},{"key":"4517_CR70","doi-asserted-by":"publisher","first-page":"107545","DOI":"10.1016\/j.jsb.2020.107545","volume":"211","author":"K Ramlaul","year":"2020","unstructured":"Ramlaul, K., Palmer, C. M., Nakane, T. & Aylett, C. H. S. Mitigating local over-fitting during single particle reconstruction with SIDESPLITTER. J. Struct. Biol. 211, 107545 (2020).","journal-title":"J. Struct. Biol."},{"key":"4517_CR71","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/nmeth.2727","volume":"11","author":"A Kucukelbir","year":"2014","unstructured":"Kucukelbir, A., Sigworth, F. J. & Tagare, H. D. Quantifying the local resolution of cryo-EM density maps. Nat. Methods 11, 63\u201365 (2014).","journal-title":"Nat. Methods"},{"key":"4517_CR72","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00782-3","volume":"8","author":"K Naydenova","year":"2017","unstructured":"Naydenova, K. & Russo, C. J. Measuring the effects of particle orientation to improve the efficiency of electron cryomicroscopy. Nat. Commun. 8, 629 (2017).","journal-title":"Nat. Commun."},{"key":"4517_CR73","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1002\/pro.3235","volume":"27","author":"TD Goddard","year":"2018","unstructured":"Goddard, T. D. et al. UCSF ChimeraX: meeting modern challenges in visualization and analysis. Protein Sci. 27, 14\u201325 (2018).","journal-title":"Protein Sci."},{"key":"4517_CR74","doi-asserted-by":"publisher","first-page":"W296","DOI":"10.1093\/nar\/gky427","volume":"46","author":"A Waterhouse","year":"2018","unstructured":"Waterhouse, A. et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 46, W296\u2013W303 (2018).","journal-title":"Nucleic Acids Res."},{"key":"4517_CR75","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1021\/ci00057a005","volume":"28","author":"D Weininger","year":"1988","unstructured":"Weininger, D. SMILES, a chemical language and information system. 1. Introduction to methodology and encoding rules. J. Chem. Inf. Comput. Sci. 28, 31\u201336 (1988).","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"4517_CR76","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1107\/S0907444904019158","volume":"60","author":"P Emsley","year":"2004","unstructured":"Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126\u20132132 (2004).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"4517_CR77","doi-asserted-by":"publisher","first-page":"2487","DOI":"10.1107\/S1399004714016241","volume":"70","author":"RA Nicholls","year":"2014","unstructured":"Nicholls, R. A., Fischer, M., McNicholas, S. & Murshudov, G. N. Conformation-independent structural comparison of macromolecules with ProSMART. Acta Crystallogr. D Biol. Crystallogr. 70, 2487\u20132499 (2014).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"4517_CR78","doi-asserted-by":"publisher","first-page":"14559","DOI":"10.1021\/bi9914457","volume":"38","author":"SA Forman","year":"1999","unstructured":"Forman, S. A. A hydrophobic photolabel inhibits nicotinic acetylcholine receptors via open-channel block following a slow step. Biochemistry 38, 14559\u201314564 (1999).","journal-title":"Biochemistry"},{"key":"4517_CR79","doi-asserted-by":"publisher","unstructured":"Sente, A. & Naydenova, K. Scripts for differential assembly diversifies GABAA receptor structures and signaling (v1.0.1). Zenodo https:\/\/doi.org\/10.5281\/zenodo.5884871 (2022).","DOI":"10.5281\/zenodo.5884871"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41586-022-04517-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-022-04517-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-022-04517-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T10:28:09Z","timestamp":1666348089000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-022-04517-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,30]]},"references-count":79,"journal-issue":{"issue":"7904","published-print":{"date-parts":[[2022,4,7]]}},"alternative-id":["4517"],"URL":"https:\/\/doi.org\/10.1038\/s41586-022-04517-3","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,30]]},"assertion":[{"value":"10 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}