Structure of a human synaptic GABA
| Autor: | Richard M. Walsh, Ryan E. Hibbs, Jinfeng Teng, Shaotong Zhu, Colleen M. Noviello, Jeong Joo Kim |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Flumazenil Models Molecular Glycosylation medicine.drug_class Benzodiazepine overdose Neurotransmission Bicuculline Ligands Binding Competitive Article 03 medical and health sciences chemistry.chemical_compound Benzodiazepines Immunoglobulin Fab Fragments GABA receptor medicine Humans Receptor Neurotransmitter GABA Modulators gamma-Aminobutyric Acid Brain Chemistry Benzodiazepine Multidisciplinary GABAA receptor business.industry Cell Membrane Cryoelectron Microscopy medicine.disease Receptors GABA-A 3. Good health 030104 developmental biology HEK293 Cells nervous system chemistry business Neuroscience medicine.drug |
| Zdroj: | Nature |
| ISSN: | 1476-4687 |
| Popis: | Fast inhibitory neurotransmission in the brain is principally mediated by the neurotransmitter GABA (γ-aminobutyric acid) and its synaptic target, the type A GABA receptor (GABAA receptor). Dysfunction of this receptor results in neurological disorders and mental illnesses including epilepsy, anxiety and insomnia. The GABAA receptor is also a prolific target for therapeutic, illicit and recreational drugs, including benzodiazepines, barbiturates, anaesthetics and ethanol. Here we present high-resolution cryo-electron microscopy structures of the human α1β2γ2 GABAA receptor, the predominant isoform in the adult brain, in complex with GABA and the benzodiazepine site antagonist flumazenil, the first-line clinical treatment for benzodiazepine overdose. The receptor architecture reveals unique heteromeric interactions for this important class of inhibitory neurotransmitter receptor. This work provides a template for understanding receptor modulation by GABA and benzodiazepines, and will assist rational approaches to therapeutic targeting of this receptor for neurological disorders and mental illness. |
| Databáze: | OpenAIRE |
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