| First Author | Zhu S | Year | 2018 |
| Journal | Nature | Volume | 559 |
| Issue | 7712 | Pages | 67-72 |
| PubMed ID | 29950725 | Mgi Jnum | J:320132 |
| Mgi Id | MGI:6869971 | Doi | 10.1038/s41586-018-0255-3 |
| Citation | Zhu S, et al. (2018) Structure of a human synaptic GABAA receptor. Nature 559(7712):67-72 |
| abstractText | Fast inhibitory neurotransmission in the brain is principally mediated by the neurotransmitter GABA (gamma-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 alpha1beta2gamma2 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. |
