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-Structure paper
Title | Structure of a human synaptic GABA receptor. |
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Journal, issue, pages | Nature, Vol. 559, Issue 7712, Page 67-72, Year 2018 |
Publish date | Jun 27, 2018 |
Authors | Shaotong Zhu / Colleen M Noviello / Jinfeng Teng / Richard M Walsh / Jeong Joo Kim / Ryan E Hibbs / |
PubMed Abstract | 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 (GABA receptor). ...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 (GABA receptor). Dysfunction of this receptor results in neurological disorders and mental illnesses including epilepsy, anxiety and insomnia. The GABA 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 GABA 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. |
External links | Nature / PubMed:29950725 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.86 - 3.92 Å |
Structure data | |
Chemicals | ChemComp-NAG: ChemComp-ABU: ChemComp-Y01: ChemComp-FYP: |
Source |
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Keywords | TRANSPORT PROTEIN / Ligand-gated ion channel / GABA-A receptor / Cys-loop receptor |