6D6U

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

6D6U の概要

• エントリーDOI: 10.2210/pdb6d6u/pdb
• EMDBエントリー: 7817
• 分子名称: Gamma-aminobutyric acid receptor subunit beta-2,Gamma-aminobutyric acid receptor subunit beta-2, GAMMA-AMINO-BUTANOIC ACID, CHOLESTEROL HEMISUCCINATE, ... (12 entities in total)
• 機能のキーワード: ligand-gated ion channel, gaba-a receptor, cys-loop receptor, transport protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 363428.24

構造登録者

Zhu, S.,Noviello, C.M.,Teng, J.,Walsh Jr, R.M.,Kim, J.J.,Hibbs, R.E. (登録日: 2018-04-22, 公開日: 2018-06-27, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.92 Å)