6D6U

Human GABA-A receptor alpha1-beta2-gamma2 subtype in complex with GABA and flumazenil, conformation A

Summary for 6D6U

• Entry DOI: 10.2210/pdb6d6u/pdb
• EMDB information: 7817
• Descriptor: Gamma-aminobutyric acid receptor subunit beta-2,Gamma-aminobutyric acid receptor subunit beta-2, GAMMA-AMINO-BUTANOIC ACID, CHOLESTEROL HEMISUCCINATE, ... (12 entities in total)
• Functional Keywords: ligand-gated ion channel, gaba-a receptor, cys-loop receptor, transport protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 9
• Total formula weight: 363428.24

Authors

Zhu, S.,Noviello, C.M.,Teng, J.,Walsh Jr, R.M.,Kim, J.J.,Hibbs, R.E. (deposition date: 2018-04-22, release date: 2018-06-27, Last modification date: 2024-11-06)

Primary citation

Zhu, S.,Noviello, C.M.,Teng, J.,Walsh, R.M.,Kim, J.J.,Hibbs, R.E.
Structure of a human synaptic GABAAreceptor.
Nature, 559:67-72, 2018

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). 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.

PubMed: 29950725
DOI: 10.1038/s41586-018-0255-3

Experimental method

ELECTRON MICROSCOPY (3.92 Å)