ArticleProceedings of the National Academy of Sciences of the United States of America2012
Pentameric ligand-gated ion channel ELIC is activated by GABA and modulated by benzodiazepines.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 129 citations in OpenAlex.
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- Origin of acetylcholine antagonism in ELIC, a bacterial pentameric ligand-gated ion channel.Communications biology · 2022Article
- The Case for Clinical Trials with Novel GABAergic Drugs in Diabetes Mellitus and Obesity.Life (Basel, Switzerland) · 2022Article
- New Insights into the Structure-Activity Relationship and Neuroprotective Profile of Benzodiazepinone Derivatives ofJournal of medicinal chemistry · 2021Article
- Selective actions of benzodiazepines at the transmembrane anaesthetic binding sites of the GABABritish journal of pharmacology · 2021Article
- Probing solution structure of the pentameric ligand-gated ion channel GLIC by small-angle neutron scattering.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Regulation of a pentameric ligand-gated ion channel by a semiconserved cationic lipid-binding site.The Journal of biological chemistry · 2021Article
- Ion Channels in Anesthesia.Advances in experimental medicine and biology · 2021Article
- Structural evidence for the binding of monocarboxylates and dicarboxylates at pharmacologically relevant extracellular sites of a pentameric ligand-gated ion channel.Acta crystallographica. Section D, Structural biology · 2020Article
- Structural basis for allosteric transitions of a multidomain pentameric ligand-gated ion channel.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Distinct Evolutionary Trajectories of Neuronal and Hair Cell Nicotinic Acetylcholine Receptors.Molecular biology and evolution · 2020Article
- Modulation of theeLife · 2020Article
- Cryo-EM structures of a lipid-sensitive pentameric ligand-gated ion channel embedded in a phosphatidylcholine-only bilayer.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- A lipid site shapes the agonist response of a pentameric ligand-gated ion channel.Nature chemical biology · 2019Article
- Determination of Ligand Profiles forInternational journal of molecular sciences · 2019Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 9 institutions in 7 countries.
Funding
Abstract
GABA(A) receptors are pentameric ligand-gated ion channels involved in fast inhibitory neurotransmission and are allosterically modulated by the anxiolytic, anticonvulsant, and sedative-hypnotic benzodiazepines. Here we show that the prokaryotic homolog ELIC also is activated by GABA and is modulated by benzodiazepines with effects comparable to those at GABA(A) receptors. Crystal structures reveal important features of GABA recognition and indicate that benzodiazepines, depending on their concentration, occupy two possible sites in ELIC. An intrasubunit site is adjacent to the GABA-recognition site but faces the channel vestibule. A second intersubunit site partially overlaps with the GABA site and likely corresponds to a low-affinity benzodiazepine-binding site in GABA(A) receptors that mediates inhibitory effects of the benzodiazepine flurazepam. Our study offers a structural view how GABA and benzodiazepines are recognized at a GABA-activated ion channel.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.