Crystal structures of a GABAA-receptor chimera reveal new endogenous neurosteroid-binding sites.
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γ-Aminobutyric acid receptors (GABA A Rs) are vital for controlling excitability in the brain. This is emphasized by the numerous neuropsychiatric disorders that result from receptor dysfunction. A critical component of most native GABA A Rs is the α subunit. Its transmembrane domain is the target for many modulators, including endogenous brain neurosteroids that impact anxiety, stress and depression, and for therapeutic drugs, such as general anesthetics. Understanding the basis for the modulation of GABA A R function requires high-resolution structures. Here we present the first atomic structures of a GABA A R chimera at 2.8-Å resolution, including those bound with potentiating and inhibitory neurosteroids. These structures define new allosteric binding sites for these modulators that are associated with the α-subunit transmembrane domain. Our findings will enable the exploitation of neurosteroids for therapeutic drug design to regulate GABA A Rs in neurological disorders.
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Cites
Trott, O., & Olson, A. J. (2010) · Journal of Computational Chemistry · doi:10.1002/jcc.21334 · Cited by 38,412 · see citing works
Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems
Darden, T., York, D., & Pedersen, L. (1993) · The Journal of Chemical Physics · doi:10.1063/1.464397 · Cited by 29,588 · see citing works
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. D. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 27,510 · see citing works
<i>Phaser</i> crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612 · see citing works
Ryckaert, J., Ciccotti, G., & Berendsen, H. (1977) · Journal of Computational Physics · doi:10.1016/0021-9991(77)90098-5 · Cited by 19,525 · see citing works
<i>MolProbity</i> : all-atom structure validation for macromolecular crystallography
Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909042073 · Cited by 14,115 · see citing works
Comparative Protein Modelling by Satisfaction of Spatial Restraints
Šali, A., & Blundell, T. L. (1993) · Journal of Molecular Biology · doi:10.1006/jmbi.1993.1626 · Cited by 12,977 · see citing works
Overview of the <i>CCP</i> 4 suite and current developments
Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P. R., Keegan, R. M., Krissinel, E. B., Leslie, A. G. W., McCoy, A., et al. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910045749 · Cited by 12,353 · see citing works
ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB
Maier, J., Martinez, C., Kasavajhala, K., Wickstrom, L., Hauser, K., & Simmerling, C. L. (2015) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.5b00255 · Cited by 10,971 · see citing works
PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical p K a Predictions
Olsson, M. H. M., Søndergaard, C. R., Rostkowski, M., & Jensen, J. H. (2011) · Journal of Chemical Theory and Computation · doi:10.1021/ct100578z · Cited by 4,482 · see citing works
Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors
Farrant, M., & Nusser, Z. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1625 · Cited by 2,081 · see citing works
The Buccaneer software for automated model building. 1. Tracing protein chains
Cowtan, K. D. (2006) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444906022116 · Cited by 1,834 · see citing works
HOLE: A program for the analysis of the pore dimensions of ion channel structural models
Smart, O. S., Neduvelil, J. G., Wang, X., Wallace, B. A., & Sansom, M. S. P. (1996) · Journal of Molecular Graphics · doi:10.1016/s0263-7855(97)00009-x · Cited by 1,803 · see citing works
Terwilliger, T. C., Grosse-Kunstleve, R. W., Afonine, P. V., Moriarty, N. W., Zwart, P. H., Hung, L.-W., Read, R. J., & Adams, P. D. (2008) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s090744490705024x · Cited by 1,462 · see citing works
General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal
Franks, N. P. (2008) · Nature reviews. Neuroscience · doi:10.1038/nrn2372 · Cited by 1,266 · see citing works
Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors
Mihic, S. J., Ye, Q., Wick, M. J., Koltchine, V. V., Krasowski, M. D., Finn, S. E., Mascia, M. P., Valenzuela, C. F., Hanson, K. K., Greenblatt, E. P., et al. (1997) · Nature · doi:10.1038/38738 · Cited by 1,219 · see citing works
Lipid14: The Amber Lipid Force Field
Dickson, C. J., Madej, B. D., Skjevik, Å. A., Betz, R. M., Teigen, K., Gould, I. R., & Walker, R. C. (2014) · Journal of Chemical Theory and Computation · doi:10.1021/ct4010307 · Cited by 1,210 · see citing works
Neurosteroids: endogenous regulators of the GABAA receptor
Belelli, D., & Lambert, J. J. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1703 · Cited by 1,159 · see citing works
Principles of activation and permeation in an anion-selective Cys-loop receptor
Hibbs, R. E., & Gouaux, E. (2011) · Nature · doi:10.1038/nature10139 · Cited by 997 · see citing works
Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites
Hosie, A. M., Wilkins, M. E., da Silva, H. M. A., & Smart, T. G. (2006) · Nature · doi:10.1038/nature05324 · Cited by 752 · see citing works
Self-citationCrystal structure of a human GABAA receptor
Miller, P. S., & Aricescu, A. R. (2014) · Nature · doi:10.1038/nature13293 · Cited by 713 · see citing works
X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation
Bocquet, N., Nury, H., Baaden, M., Poupon, C. L., Changeux, J., Delarue, M. H., & Corringer, P. (2008) · Nature · doi:10.1038/nature07462 · Cited by 674 · see citing works
Desensitized states prolong GABAA channel responses to brief agonist pulses
Jones, M. V., & Westbrook, G. L. (1995) · Neuron · doi:10.1016/0896-6273(95)90075-6 · Cited by 584 · see citing works
Winter, G., Lobley, C. M. C., & Prince, S. M. (2013) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444913015308 · Cited by 567 · see citing works
Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel
Hilf, R. J. C., & Dutzler, R. (2008) · Nature · doi:10.1038/nature07461 · Cited by 526 · see citing works
X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel
Nury, H., Van Renterghem, C., Weng, Y., Tran, A., Baaden, M., Dufresne, V., Changeux, J.-P., Sonner, J. M., Delarue, M., & Corringer, P.-J. (2011) · Nature · doi:10.1038/nature09647 · Cited by 412 · see citing works
Glycine receptor mechanism illuminated by electron cryo-microscopy
Du, J., Lu, W., Wu, S.-P., Cheng, Y.-F., & Gouaux, E. (2015) · Nature · doi:10.1038/nature14853 · Cited by 408 · see citing works
X-ray structure of the human α4β2 nicotinic receptor
Morales-Pérez, C. L., Noviello, C., & Hibbs, R. E. (2016) · Nature · doi:10.1038/nature19785 · Cited by 396 · see citing works
Fritschy, J., & Brünig, I. (2003) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(03)00037-8 · Cited by 322 · see citing works
Rudolph, U., & Möhler, H. (2014) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011613-135947 · Cited by 319 · see citing works
Coupling of agonist binding to channel gating in the GABAA receptor
Kash, T. L., Jenkins, A., Kelley, J. C., Trudell, J. R., & Harrison, N. L. (2003) · Nature · doi:10.1038/nature01280 · Cited by 312 · see citing works
A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family
Bocquet, N., de Carvalho, L. P., Cartaud, J., Neyton, J., Poupon, C. L., Taly, A., Grütter, T., Changeux, J., & Corringer, P. (2006) · Nature · doi:10.1038/nature05371 · Cited by 309 · see citing works
Binding, activation and modulation of Cys-loop receptors
Miller, P. S., & Smart, T. G. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.12.005 · Cited by 299 · see citing works
Self-citationThe GABAA Receptor as a Therapeutic Target for Neurodevelopmental Disorders
Braat, S., & Kooy, R. F. (2015) · Neuron · doi:10.1016/j.neuron.2015.03.042 · Cited by 294 · see citing works
Li, G., Chiara, D. C., Sawyer, G. W., Husain, S. S., Olsen, R. W., & Cohen, J. B. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3467-06.2006 · Cited by 289 · see citing works
Neurotransmitter action: Opening of ligand-gated ion channels
Unwin, N. (1993) · Cell · doi:10.1016/s0092-8674(05)80026-1 · Cited by 273 · see citing works
Distinguishing Between GABAA Receptors Responsible for Tonic and Phasic Conductances
Módy, I. (2001) · Neurochemical Research · doi:10.1023/a:1012376215967 · Cited by 261 · see citing works
X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors
Althoff, T., Hibbs, R. E., Banerjee, S., & Gouaux, E. (2014) · Nature · doi:10.1038/nature13669 · Cited by 251 · see citing works
Pei, J., & Grishin, N. V. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-646-7_17 · Cited by 241 · see citing works
Structure and Pharmacology of Pentameric Receptor Channels: From Bacteria to Brain
Corringer, P., Poitevin, F., Prevost, M. S., Sauguet, L., Delarue, M. H., & Changeux, J. (2012) · Structure · doi:10.1016/j.str.2012.05.003 · Cited by 237 · see citing works
Crystal structure of human glycine receptor-α3 bound to antagonist strychnine
Huang, X. Y., Chen, H., Michelsen, K., Schneider, S., & Shaffer, P. L. (2015) · Nature · doi:10.1038/nature14972 · Cited by 230 · see citing works
Neurosteroid binding sites on GABAA receptors
Hosie, A. M., Wilkins, M. E., & Smart, T. G. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.03.011 · Cited by 219 · see citing works
Self-citationStructural basis for ion permeation mechanism in pentameric ligand‐gated ion channels
Sauguet, L., Poitevin, F., Murail, S., Renterghem, C. V., Moraga‐Cid, G., Malherbe, L., Thompson, A., Koehl, P., Corringer, P., Baaden, M., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.17 · Cited by 147 · see citing works
Neurosteroid Replacement Therapy for Catamenial Epilepsy
Reddy, D. S., & Rogawski, M. A. (2009) · Neurotherapeutics · doi:10.1016/j.nurt.2009.01.006 · Cited by 144 · see citing works
The desensitization gate of inhibitory Cys-loop receptors
Gielen, M. C., Thomas, P., & Smart, T. G. (2015) · Nature Communications · doi:10.1038/ncomms7829 · Cited by 135 · see citing works
Self-citationStructural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel
Sauguet, L., Howard, R. J., Malherbe, L., Lee, U. S., Corringer, P., Harris, R. A., & Delarue, M. H. (2013) · Nature Communications · doi:10.1038/ncomms2682 · Cited by 132 · see citing works
Schmidt, T. H., & Kandt, C. (2012) · Journal of Chemical Information and Modeling · doi:10.1021/ci3000453 · Cited by 129 · see citing works
Crystal structures of human glycine receptor α3 bound to a novel class of analgesic potentiators
Huang, X. Y., Shaffer, P. L., Ayube, S., Bregman, H. S., Chen, H., Lehto, S. G., Luther, J. A., Matson, D. J., McDonough, S. I., Michelsen, K., et al. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3329 · Cited by 120 · see citing works
Rüsch, D., Zhong, H., & Forman, S. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400472200 · Cited by 114 · see citing works
Structural basis for alcohol modulation of a pentameric ligand-gated ion channel
Howard, R. J., Murail, S., Ondricek, K. E., Corringer, P., Lindahl, E. R., Trudell, J. R., & Harris, R. A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1104480108 · Cited by 106 · see citing works
Bright, D. P., Renzi, M., Bartram, J., McGee, T. P., MacKenzie, G., Hosie, A. M., Farrant, M., & Brickley, S. G. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2996-10.2011 · Cited by 98 · see citing works
Akk, G., Li, P., Bracamontes, J. R., Reichert, D. E. C., Covey, D. F., & Steinbach, J. H. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.048520 · Cited by 92 · see citing works
Covey, D. F., Nathan, D., Kalkbrenner, M., Nilsson, K. R., Hu, Y., Zorumski, C. F., & Evers, A. S. (2000) · PubMed · Cited by 92 · see citing works
De novo GABRA1 mutations in Ohtahara and West syndromes
Kodera, H., Ohba, C., Kato, M., Maeda, T., Araki, K., Tajima, D., Matsuo, M., Hino‐Fukuyo, N., 小橋, 孝., Ishiyama, A., et al. (2016) · Epilepsia · doi:10.1111/epi.13344 · Cited by 91 · see citing works
Crystal Structures of Human GlyRα3 Bound to Ivermectin
Huang, X. Y., Chen, H., & Shaffer, P. L. (2017) · Structure · doi:10.1016/j.str.2017.04.007 · Cited by 88 · see citing works
A Predicted Binding Site for Cholesterol on the GABAA Receptor
Hénin, J., Salari, R., Murlidaran, S., & Brannigan, G. H. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2014.03.024 · Cited by 84 · see citing works
Two WXXF‐based motifs in NECAPs define the specificity of accessory protein binding to AP‐1 and AP‐2
Ritter, B., Denisov, A. Y., Philie, J., Deprez, C., Tung, E. C., Gehring, K., & McPherson, P. S. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600378 · Cited by 73 · see citing works
Chen, Z.-W., Manion, B., Townsend, R. R., Reichert, D. E., Covey, D. F., Steinbach, J. H., Sieghart, W., Fuchs, K., & Evers, A. S. (2012) · Molecular Pharmacology · doi:10.1124/mol.112.078410 · Cited by 72 · see citing works
Li, G., Chiara, D. C., Cohen, J. B., & Olsen, R. W. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.c900016200 · Cited by 71 · see citing works
Desensitization Mechanism in Prokaryotic Ligand-gated Ion Channel
Velisetty, P., & Chakrapani, S. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.348045 · Cited by 64 · see citing works
González-Gutiérrez, G., & Grosman, C. F. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.09.026 · Cited by 63 · see citing works
Enantioselectivity of Pregnanolone-Induced γ-Aminobutyric AcidA Receptor Modulation and Anesthesia
Covey, D. F., Nathan, D., Kalkbrenner, M., Nilsson, K. R., Hu, Y., Zorumski, C. F., & Evers, A. S. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39327-9 · Cited by 62 · see citing works
Effect of the α subunit subtype on the macroscopic kinetic properties of recombinant GABAA receptors
Picton, A. J., & Fisher, J. L. (2007) · Brain Research · doi:10.1016/j.brainres.2007.06.050 · Cited by 61 · see citing works
Making sense of nonsense GABAA receptor mutations associated with genetic epilepsies
Kang, J., & Macdonald, R. L. (2009) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2009.07.003 · Cited by 60 · see citing works
Moraga‐Cid, G., Sauguet, L., Huon, C., Malherbe, L., Girard-Blanc, C., Pêtres, S., Murail, S., Taly, A., Baaden, M., Delarue, M. H., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417864112 · Cited by 49 · see citing works
Hales, T. G., Deeb, T. Z., Tang, H., Bollan, K. A., King, D. P., Johnson, S., & Connolly, C. N. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603599200 · Cited by 39 · see citing works
Identification of a beta subunit TM2 residue mediating proton modulation of GABA type A receptors.
Wilkins, M. E., Hosie, A. M., & Smart, T. G. (2002) · PubMed Central · doi:10.1523/jneurosci.22-13-05328.2002 · Cited by 39 · see citing works
Self-citationSigel, E., Buhr, A., & Baur, R. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.731758.x · Cited by 33 · see citing works
Inhibitory Neurosteroids and the GABAA Receptor
Seljeset, S., Laverty, D. C., & Smart, T. G. (2014) · Advances in pharmacology · doi:10.1016/bs.apha.2014.10.006 · Cited by 33 · see citing works
Self-citationGenuine open form of the pentameric ligand-gated ion channel GLIC
Fourati, Z., Sauguet, L., & Delarue, M. H. (2015) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s1399004714026698 · Cited by 26 · see citing works
A neurosteroid potentiation site can be moved among GABAAreceptor subunits
Bracamontes, J. R., Li, P., Akk, G., & Steinbach, J. H. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.237255 · Cited by 21 · see citing works
nmrlipids.blogspot.fi — on October 25th 2015
The NMRlipids Collaboration, Miettinen, M. S., Ollila, O. H. S., Boţan, A., Catte, A., Edholm, O., Favela-Rosales, F., Ferreira, T. M., Fuchs, P., Girych, M., et al. (2015) · Figshare · doi:10.6084/m9.figshare.1585017 · Cited by 2 · see citing works
Flagged first, then by citations
1 of the 73 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- [7]Smart TG Paoletti P Synaptic Neurotransmitter-Gated Receptors Sheng M Sabatini BL Sudhof TC The Synapse Cold Spring Harbor Laboratory Press New York 2012 191 216
Cited by
Sorted by citations
Single-particle cryo-EM at atomic resolution
Nakane, T., Kotecha, A., Sente, A., McMullan, G., Masiulis, S., Brown, P. M. G. E., Grigoras, I. T., Malinauskaitė, L., Malinauskas, T., Miehling, J., et al. (2020) · Nature · doi:10.1038/s41586-020-2829-0 · Cited by 881 · see citing works
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686 · see citing works
Structure of a human synaptic GABAA receptor
Zhu, S., Noviello, C., Teng, J., Walsh, R. M., Kim, J. J., & Hibbs, R. E. (2018) · Nature · doi:10.1038/s41586-018-0255-3 · Cited by 555 · see citing works
Cryo-EM structure of the human α1β3γ2 GABAA receptor in a lipid bilayer
Laverty, D., Desai, R., Uchański, T., Masiulis, S., Stec, W. J., Malinauskas, T., Zivanov, J., Pardon, E., Steyaert, J., Miller, K. W., et al. (2019) · Nature · doi:10.1038/s41586-018-0833-4 · Cited by 316 · see citing works
Self-citationGABAA receptor signalling mechanisms revealed by structural pharmacology
Masiulis, S., Desai, R., Uchański, T., Martin, I. S., Laverty, D. C., Karia, D., Malinauskas, T., Zivanov, J., Pardon, E., Kotecha, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0832-5 · Cited by 559 · see citing works
Self-citationNeurosteroids as novel antidepressants and anxiolytics: GABA-A receptors and beyond
Zorumski, C. F., Paul, S. M., Covey, D. F., & Mennerick, S. (2019) · Neurobiology of Stress · doi:10.1016/j.ynstr.2019.100196 · Cited by 305 · see citing works
Effect of Zuranolone vs Placebo in Postpartum Depression
Deligiannidis, K. M., Meltzer-Brody, S., Gunduz-Bruce, H., Doherty, J., Jonas, J., Li, S., Sankoh, A. J., Silber, C., Campbell, A. D., Werneburg, B., et al. (2021) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2021.1559 · Cited by 277 · see citing works
Towards a comprehensive understanding of anesthetic mechanisms of action: a decade of discovery
Hemmings, H. C., Riegelhaupt, P. M., Kelz, M. B., Solt, K., Eckenhoff, R. G., Orser, B. A., & Goldstein, P. A. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.05.001 · Cited by 244 · see citing works
Structural principles of distinct assemblies of the human α4β2 nicotinic receptor
Walsh, R. M., Roh, S., Gharpure, A., Morales-Pérez, C. L., Teng, J., & Hibbs, R. E. (2018) · Nature · doi:10.1038/s41586-018-0081-7 · Cited by 226 · see citing works
Sieghart, W., & Savić, M. M. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014449 · Cited by 211 · see citing works
Duncan, A. L., Song, W., & Sansom, M. S. P. (2020) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010919-023411 · Cited by 158 · see citing works
Direct Structural Insights into GABAA Receptor Pharmacology
Kim, J. J., & Hibbs, R. E. (2021) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2021.01.011 · Cited by 139 · see citing works
Althaus, A. L., Ackley, M. A., Belfort, G. M., Gee, S. M., Dai, J., Nguyen, D. P., Kazdoba, T. M., Modgil, A., Davies, P. A., Moss, S. J., et al. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108333 · Cited by 135 · see citing works
Allopregnanolone in postpartum depression: Role in pathophysiology and treatment
Meltzer-Brody, S. E., & Kanes, S. (2020) · Neurobiology of Stress · doi:10.1016/j.ynstr.2020.100212 · Cited by 133 · see citing works
The dual‐gate model for pentameric ligand‐gated ion channels activation and desensitization
Gielen, M., & Corringer, P. (2018) · Journal of Physiology · doi:10.1113/jp275100 · Cited by 111 · see citing works
Self-citationLüscher, B., & Möhler, H. (2019) · F1000Research · doi:10.12688/f1000research.18758.1 · Cited by 105 · see citing works
García‐Nafría, J., & Tate, C. G. (2019) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010919-023545 · Cited by 116 · see citing works
GABAA receptors as targets for treating affective and cognitive symptoms of depression
Lüscher, B., Maguire, J. L., Rudolph, U., & Sibille, E. L. (2023) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2023.06.009 · Cited by 119 · see citing works
Allopregnanolone-based treatments for postpartum depression: Why/how do they work?
Walton, N., & Maguire, J. (2019) · Neurobiology of Stress · doi:10.1016/j.ynstr.2019.100198 · Cited by 103 · see citing works
Multiple functional neurosteroid binding sites on GABAA receptors
Chen, Z.-W., Bracamontes, J. R., Budelier, M. M., Germann, A. L., Shin, D. J., Krishnan, K., Qian, M., Manion, B. D., Cheng, W. W. L., Reichert, D. E. C., et al. (2019) · PLoS Biology · doi:10.1371/journal.pbio.3000157 · Cited by 99 · see citing works
Cryo-EM structures reveal native GABAA receptor assemblies and pharmacology
Sun, C. L., Zhu, H., Clark, S., & Gouaux, E. (2023) · Nature · doi:10.1038/s41586-023-06556-w · Cited by 91 · see citing works
Conformational transitions and ligand-binding to a muscle-type nicotinic acetylcholine receptor
Zarkadas, E., Pebay‐Peyroula, E., Thompson, M. J., Schoehn, G., Uchański, T., Steyaert, J., Chipot, C. J., Dehez, F., Baenziger, J. E., & Nury, H. (2022) · Neuron · doi:10.1016/j.neuron.2022.01.013 · Cited by 85 · see citing works
Bixo, M., Johansson, M., Timby, E., Michalski, L., & Bäckström, T. C. (2017) · Journal of Neuroendocrinology · doi:10.1111/jne.12553 · Cited by 83 · see citing works
ATP7A-Regulated Enzyme Metalation and Trafficking in the Menkes Disease Puzzle
Horn, N., & Wittung-Stafshede, P. E. (2021) · Biomedicines · doi:10.3390/biomedicines9040391 · Cited by 79 · see citing works
Structural insights into opposing actions of neurosteroids on GABAA receptors
Legesse, D., Fan, C., Teng, J., Zhuang, Y., Howard, R. J., Noviello, C., Lindahl, E. R., & Hibbs, R. E. (2023) · Nature Communications · doi:10.1038/s41467-023-40800-1 · Cited by 75 · see citing works
Structural basis of neurosteroid anesthetic action on GABAA receptors
Chen, Q., Wells, M. M., Arjunan, P., Tillman, T. S., Cohen, A. E., Xu, Y., & Tang, P. S. (2018) · Nature Communications · doi:10.1038/s41467-018-06361-4 · Cited by 79 · see citing works
A structural perspective on GABAA receptor pharmacology
Scott, S., & Aricescu, A. R. (2019) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2019.03.023 · Cited by 79 · see citing works
Patterson, R., Balan, I. S., Morrow, A. L., & Meltzer-Brody, S. E. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01721-1 · Cited by 81 · see citing works
Cryo-EM: the resolution revolution and drug discovery
de Oliveira, T. M., van Beek, L., Shilliday, F., Debreczeni, J. É., & Phillips, C. (2021) · SLAS DISCOVERY · doi:10.1177/2472555220960401 · Cited by 73 · see citing works
Rationalizing Steroid Interactions with Lipid Membranes: Conformations, Partitioning, and Kinetics
Atkovska, K., Klingler, J., Oberwinkler, J., Keller, S., & Hub, J. S. (2018) · ACS Central Science · doi:10.1021/acscentsci.8b00332 · Cited by 71 · see citing works
Szlenk, C. T., GC, J. B., & Natesan, S. (2019) · Molecular Pharmacology · doi:10.1124/mol.118.115113 · Cited by 67 · see citing works
Lloyd‐Evans, E., & Waller‐Evans, H. (2020) · Essays in Biochemistry · doi:10.1042/ebc20200043 · Cited by 71 · see citing works
A lipid site shapes the agonist response of a pentameric ligand-gated ion channel
Hénault, C. M., Govaerts, C., Spurný, R., Brams, M., Estrada‐Mondragón, A., Lynch, J. W., Bertrand, D., Pardon, E., Evans, G. L., Woods, K., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0369-4 · Cited by 61 · see citing works
A half century of γ-aminobutyric acid
Smart, T. G., & Stephenson, F. A. (2019) · Brain and Neuroscience Advances · doi:10.1177/2398212819858249 · Cited by 63 · see citing works
Self-citationSite-specific effects of neurosteroids on GABAA receptor activation and desensitization
Sugasawa, Y., Cheng, W. W. L., Bracamontes, J. R., Chen, Z.-W., Wang, L., Germann, A. L., Pierce, S. R., Senneff, T. C., Krishnan, K., Reichert, D. E. C., et al. (2020) · eLife · doi:10.7554/elife.55331 · Cited by 61 · see citing works
From bugs to brain: unravelling the GABA signalling networks in the brain–gut–microbiome axis
Belelli, D., Lambert, J. J., Wan, M. L. Y., Monteiro, A. R., Nutt, D., & Swinny, J. D. (2024) · Brain · doi:10.1093/brain/awae413 · Cited by 67 · see citing works
Kasaragod, V. B., & Schindelin, H. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00317 · Cited by 60 · see citing works
SULFATION PATHWAYS: Insights into steroid sulfation and desulfation pathways
Foster, P., & Mueller, J. W. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-18-0086 · Cited by 57 · see citing works
Castellano, D., Shepard, R. D., & Lü, W. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.616298 · Cited by 53 · see citing works
Regulation of GABAA receptors by prolonged exposure to endogenous and exogenous ligands
Gravielle, M. C. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.05.015 · Cited by 50 · see citing works
Yamato, K., Nakata, Y., Takashima, M., Ozoe, F., Asahi, M., Kobayashi, M., & Ozoe, Y. (2019) · Pesticide Biochemistry and Physiology · doi:10.1016/j.pestbp.2019.11.001 · Cited by 50 · see citing works
Parakala, M. L., Zhang, Y., Modgil, A., Chadchankar, J., Vien, T. N., Ackley, M. A., Doherty, J., Davies, P. A., & Moss, S. J. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.008875 · Cited by 49 · see citing works
Elephants in the Dark: Insights and Incongruities in Pentameric Ligand-gated Ion Channel Models
Howard, R. J. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167128 · Cited by 45 · see citing works
The desensitization pathway of GABAA receptors, one subunit at a time
Gielen, M. C., Barilone, N., & Corringer, P. (2020) · Nature Communications · doi:10.1038/s41467-020-19218-6 · Cited by 40 · see citing works
Self-citationGABA(A) receptor-targeted drug development -New perspectives in perioperative anesthesia
Antkowiak, B., & Rammes, G. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1599356 · Cited by 39 · see citing works
The interaction of steroids with phospholipid bilayers and membranes
Crowley, J., Withana, M., & Deplazes, E. (2021) · Biophysical Reviews · doi:10.1007/s12551-021-00918-2 · Cited by 37 · see citing works
Extrasynaptic δ-subunit containing GABAA receptors
Arslan, A. (2021) · Journal of Integrative Neuroscience · doi:10.31083/j.jin.2021.01.284 · Cited by 36 · see citing works
Field, M., Dorovykh, V., Thomas, P., & Smart, T. G. (2021) · Nature Communications · doi:10.1038/s41467-021-22420-9 · Cited by 36 · see citing works
Self-citationReddy, D. S. (2023) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.123.001816 · Cited by 34 · see citing works
Alanis, B. A. V., Iorio, M. T., Silva, L., Bampali, K., Ernst, M. C., Schnürch, M., & Mihovilovič, M. D. (2020) · Molecules · doi:10.3390/molecules25040999 · Cited by 34 · see citing works
Dämgen, M. A., & Biggin, P. C. (2021) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1007856 · Cited by 34 · see citing works
Self-citationZeng, X., Hu, K., Chen, L., Zhou, L., Luo, W., Li, C., Zong, W., Chen, S., Gao, Q., Zeng, G., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01020 · Cited by 34 · see citing works
Conformational transitions and allosteric modulation in a heteromeric glycine receptor
Gibbs, E., Klemm, E., Seiferth, D., Kumar, A., Ilca, S., Biggin, P., & Chakrapani, S. (2023) · Nature Communications · doi:10.1038/s41467-023-37106-7 · Cited by 33 · see citing works
Self-citationStructural basis for the modulation of pentameric ligand-gated ion channel function by lipids
Thompson, M. J., & Baenziger, J. E. (2020) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2020.183304 · Cited by 32 · see citing works
Mapping two neurosteroid-modulatory sites in the prototypic pentameric ligand-gated ion channel GLIC
Cheng, W. W. L., Chen, Z.-W., Bracamontes, J. R., Budelier, M. M., Krishnan, K., Shin, D. J., Wang, C., Jiang, X. Q., Covey, D. F., Akk, G., et al. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.000359 · Cited by 28 · see citing works
Neurosteroid enantiomers as potentially novel neurotherapeutics
Covey, D. F., Evers, A. S., Izumi, Y., Maguire, J. L., Mennerick, S. J., & Zorumski, C. F. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105191 · Cited by 29 · see citing works
Feng, H.-J., & Forman, S. A. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.12.031 · Cited by 29 · see citing works
Zhang, Y., Wang, K., & Yu, Z. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01304 · Cited by 29 · see citing works
Model of Environmental Membrane Field for Transmembrane Proteins
Roterman, I., Stąpor, K., Fabian, P., Konieczny, L., & Banach, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073619 · Cited by 29 · see citing works
Filling the Gap in Understanding the Mechanism of GABAAR and Propofol Using Computational Approaches
Yuan, X., Zhang, D., Mao, S., & Wang, Q. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c01290 · Cited by 28 · see citing works
Probing GABAA receptors with inhibitory neurosteroids
Seljeset, S., Bright, D. P., Thomas, P., & Smart, T. G. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.02.008 · Cited by 27 · see citing works
Self-citationCryo-EM structure of the human α5β3 GABAA receptor
Liu, S., Xu, L., Guan, F., Liu, Y.-T., Cui, Y., Zhang, Q. H., Zheng, X., Bi, G., Zhou, Z. H., Zhang, X., et al. (2018) · Cell Research · doi:10.1038/s41422-018-0077-8 · Cited by 28 · see citing works
A photoswitchable GABA receptor channel blocker
Maleeva, G., Wutz, D., Rustler, K., Nin‐Hill, A., Rovira, C., Petukhova, E. O., Bautista-Barrufet, A., Gomila, A. M. J., Scholze, P., Peiretti, F., et al. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14689 · Cited by 28 · see citing works
New directions in neurosteroid therapeutics in neuropsychiatry
Zorumski, C. F., Covey, D. F., Izumi, Y., Evers, A. S., Maguire, J. L., & Mennerick, S. J. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106119 · Cited by 27 · see citing works
The Glycine Receptor Allosteric Ligands Library (GRALL)
Cerdan, A. H., Sisquellas, M., Pereira, G. P., Gomes, D. E. B., Changeux, J., & Cecchini, M. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa170 · Cited by 27 · see citing works
Pharmacological modulation of GABAA receptors
Knoflach, F., & Bertrand, D. (2021) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2021.04.003 · Cited by 27 · see citing works
ChemEM: Flexible Docking of Small Molecules in Cryo-EM Structures
Sweeney, A., Mulvaney, T., Maiorca, M., & Topf, M. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01134 · Cited by 26 · see citing works
Brams, M., Govaerts, C., Kambara, K., Price, K. L., Spurný, R., Gharpure, A., Pardon, E., Evans, G. L., Bertrand, D., Lummis, S. C. R., et al. (2020) · eLife · doi:10.7554/elife.51511 · Cited by 22 · see citing works
Common binding sites for cholesterol and neurosteroids on a pentameric ligand-gated ion channel
Budelier, M. M., Cheng, W. W. L., Chen, Z.-W., Bracamontes, J. R., Sugasawa, Y., Krishnan, K., Mydock-McGrane, L. K., Covey, D. F., & Evers, A. S. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2018.11.005 · Cited by 24 · see citing works
Germann, A. L., Pierce, S. R., Tateiwa, H., Sugasawa, Y., Reichert, D. E. C., Evers, A. S., Steinbach, J. H., & Akk, G. (2021) · Molecular Pharmacology · doi:10.1124/molpharm.121.000268 · Cited by 25 · see citing works
Cheng, W. W. L., Arcario, M. J., & Petroff, J. T. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2021.798102 · Cited by 24 · see citing works
Spontaneous lipid binding to the nicotinic acetylcholine receptor in a native membrane
Sharp, L., & Brannigan, G. H. (2021) · The Journal of Chemical Physics · doi:10.1063/5.0046333 · Cited by 24 · see citing works
Pierce, S. R., Germann, A. L., Steinbach, J. H., & Akk, G. (2021) · Molecular Pharmacology · doi:10.1124/molpharm.121.000385 · Cited by 24 · see citing works
Structural basis for cannabinoid-induced potentiation of alpha1-glycine receptors in lipid nanodiscs
Kumar, A., Kindig, K. J., Rao, S., Zaki, A. M., Basak, S., Sansom, M. S. P., Biggin, P. C., & Chakrapani, S. (2022) · Nature Communications · doi:10.1038/s41467-022-32594-5 · Cited by 24 · see citing works
Self-citationPositive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies
Gallagher, C. I., Ha, D. A., Harvey, R. J., & Vandenberg, R. J. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.122.000583 · Cited by 26 · see citing works
Structure of Heteropentameric GABAA Receptors and Receptor-Anchoring Properties of Gephyrin
Kasaragod, V. B., & Schindelin, H. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00191 · Cited by 24 · see citing works
Heteromeric GABA A receptor structures in positively-modulated active statesPreprint
Miller, P. S., Masiulis, S., Malinauskas, T., Kotecha, A., Rao, S., Chavali, S., Colibus, L. D., Pardon, E., Hannan, S. B., Scott, S., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/338343 · Cited by 25 · see citing works
Self-citationThe molecular basis of drug selectivity for α5 subunit-containing GABAA receptors
Kasaragod, V. B., Malinauskas, T., Wahid, A. A., Lengyel, J., Knoflach, F., Hardwick, S. W., Jones, C. F., Chen, W.-N., Lucas, X., Omari, K. E., et al. (2023) · Nature Structural & Molecular Biology · doi:10.1038/s41594-023-01133-1 · Cited by 23 · see citing works
Modulation of GABA A receptor function and sleep
Brickley, S. G., Franks, N. P., & Wisden, W. (2018) · Current Opinion in Physiology · doi:10.1016/j.cophys.2017.12.011 · Cited by 23 · see citing works
Structural determinants and regulation of spontaneous activity in GABAA receptors
Sexton, C. A., Penzinger, R., Mortensen, M., Bright, D. P., & Smart, T. G. (2021) · Nature Communications · doi:10.1038/s41467-021-25633-0 · Cited by 23 · see citing works
Self-citationHeider, J., Kilian, J., Garifulina, A. I., Hering, S., Langer, T., & Seidel, T. (2022) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.2c00814 · Cited by 22 · see citing works
Sharp, L., Salari, R., & Brannigan, G. H. (2019) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2019.01.005 · Cited by 21 · see citing works
Jayakar, S. S., Zhou, X., Chiara, D. C., Jarava‐Barrera, C., Savechenkov, P. Y., Bruzik, K. S., Tortosa, M., Miller, K. W., & Cohen, J. B. (2019) · Molecular Pharmacology · doi:10.1124/mol.118.114975 · Cited by 21 · see citing works
Tikhonova, T. A., Rassokhina, I. V., Kondrakhin, E. A., Fedosov, M. A., Bukanova, J. V., Rossokhin, A. V., Sharonova, I. N., Kovalev, G. I., Zavarzin, I. V., & Volkova, Y. A. (2019) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2019.103334 · Cited by 21 · see citing works
Regulation of a pentameric ligand-gated ion channel by a semiconserved cationic lipid-binding site
Sridhar, A., Lummis, S. C. R., Pasini, D., Mehregan, A., Brams, M., Kambara, K., Bertrand, D., Lindahl, E. R., Howard, R. J., & Ulens, C. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100899 · Cited by 18 · see citing works
Wang, L., Covey, D. F., Akk, G., & Evers, A. S. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666211202150041 · Cited by 21 · see citing works
In Search of GABAA Receptor’s Neurosteroid Binding Sites
Álvarez, L. D., Pecci, A., & Estrin, D. A. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01400 · Cited by 20 · see citing works
Bullock, A. E., Gunduz‐Bruce, H., Zammit, G. K., Qin, M., Li, H., Sankoh, A. J., Silber, C., Kanes, S., Jonas, J. M., & Doherty, J. (2021) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2806 · Cited by 20 · see citing works
Jayakar, S. S., Chiara, D. C., Zhou, X., Wu, B., Bruzik, K. S., Miller, K. W., & Cohen, J. B. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.013452 · Cited by 19 · see citing works
Delgado‐Vélez, M., Quesada, O., Villalobos‐Santos, J. C., Maldonado‐Hernández, R., Asmar-Rovira, G. A., Stevens, R. C., & Lasalde‐Dominicci, J. A. (2021) · Molecules · doi:10.3390/molecules26195753 · Cited by 19 · see citing works
The immediate and maintained effects of neurosteroids on GABAA receptors
Belelli, D., Peters, J. A., Phillips, G., & Lambert, J. J. (2022) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2022.100333 · Cited by 19 · see citing works
Hannan, S. B., & Smart, T. G. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002792 · Cited by 19 · see citing works
Self-citationThe molecular determinants of neurosteroid binding in the GABA(A) receptor
Sugasawa, Y., Bracamontes, J. R., Krishnan, K., Covey, D. F., Reichert, D. E. C., Akk, G., Chen, Q., Tang, P. S., Evers, A. S., & Cheng, W. W. L. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105383 · Cited by 19 · see citing works
Molecular mechanisms of the GABA type A receptor function
Michałowski, M. A., Kłopotowski, K., Wiera, G., Czyzewska, M. M., & Mozrzymas, J. W. (2025) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583524000179 · Cited by 18 · see citing works
Synthetic neuroactive steroids as new sedatives and anaesthetics: Back to the future
Manzella, F. M., Covey, D. F., Jevtović‐Todorović, V., & Todorovic, S. M. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.13086 · Cited by 18 · see citing works
Vogel, F. D., Krenn, M., Westphal, D. S., Graf, E., Wagner, M., Leiz, S., Koniuszewski, F., Augé-Stock, M., Kramer, G., Scholze, P., et al. (2022) · Epilepsia · doi:10.1111/epi.17188 · Cited by 17 · see citing works
Interfacial Binding Sites for Cholesterol on TRP Ion Channels
LEE, A. G. J. (2019) · Biophysical Journal · doi:10.1016/j.bpj.2019.10.011 · Cited by 18 · see citing works
Recent Insight into Lipid Binding and Lipid Modulation of Pentameric Ligand-Gated Ion Channels
Ananchenko, A., Hussein, T. O. K., Mody, D., Thompson, M. J., & Baenziger, J. E. (2022) · Biomolecules · doi:10.3390/biom12060814 · Cited by 17 · see citing works
Javaid, U., Afroz, S., Ashraf, W., Saghir, K. A., Alqahtani, F., Anjum, S. M. M., Ahmad, T., & Imran, I. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116791 · Cited by 16 · see citing works
Bartocci, A., Grazzi, A., Awad, N., Corringer, P., Souza, P. C. T., & Cecchini, M. (2024) · Nature Communications · doi:10.1038/s41467-024-53098-4 · Cited by 17 · see citing works
- Authors
- Laverty, D., Thomas, P., Field, M., Andersen, O. J., Gold, M. G., Biggin, P. C., Gielen, M., & Smart, T. G.
- Affiliations
- University College London (GB)
- University of Oxford (GB)
- Corresponding author
- Smart, Trevor G
- Venue
- Nature Structural & Molecular Biology
- Published
- 2017-10-02
- Volume
- 24
- Issue
- 11
- Pages
- 977-985
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC6853794
- OpenAlex
- W2756488677
- Cited by
- 179
- References
- 73
- Citations by year
- 2026: 11 · 2025: 7 · 2024: 15 · 2023: 19 · 2022: 14 · 2021: 31 · 2020: 21 · 2019: 33 · 2018: 26 · 2017: 2
- FWCI
- 10.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (104194/Z/14/Z, 104194)
- Medical Research Council (MR/K005537/1)
- Engineering and Physical Sciences Research Council (EP/G042853/1, EP/J003921/1, EP/M022609/1, EP/M027546/1, EP/I030395/1, EP/J010588/1, EP/G007705/1, EP/L000253/1)
- Biotechnology and Biological Sciences Research Council (BB/L018756/1, BB/K016601/1, BB/N015274/1)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- GABAA receptor, neurosteroids, allosteric site, chimeric receptors, crystal structure, general anesthetics, GABA receptor modulation, drug design
- MeSH terms
- Animals, Binding Sites, Models, Molecular, Protein Conformation, Receptors, GABA-A, Recombinant Proteins, Crystallography, X-Ray, Neurotransmitter Agents, Mice
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