6DW0

Cryo-EM structure of the benzodiazepine-sensitive alpha1beta1gamma2S tri-heteromeric GABAA receptor in complex with GABA (Whole map)

6DW0 の概要

• エントリーDOI: 10.2210/pdb6dw0/pdb
• 関連するPDBエントリー: 6DW1
• EMDBエントリー: 8922 8923
• 分子名称: Gamma-aminobutyric acid receptor subunit gamma-2, Gamma-aminobutyric acid receptor subunit alpha-1,Gamma-aminobutyric acid receptor subunit alpha-1, Gamma-aminobutyric acid receptor subunit beta-1,Gamma-aminobutyric acid receptor subunit beta-1, ... (8 entities in total)
• 機能のキーワード: neurotransmission, gaba receptors, gaba, cys loop receptors, ion channel, membrane protein
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 242410.22

構造登録者

Phulera, S.,Zhu, H.,Yu, J.,Yoshioka, C.,Gouaux, E. (登録日: 2018-06-26, 公開日: 2018-08-08, 最終更新日: 2024-11-20)

主引用文献

Phulera, S.,Zhu, H.,Yu, J.,Claxton, D.P.,Yoder, N.,Yoshioka, C.,Gouaux, E.
Cryo-EM structure of the benzodiazepine-sensitive alpha 1 beta 1 gamma 2S tri-heteromeric GABAAreceptor in complex with GABA.
Elife, 7:-, 2018

PubMed Abstract: Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Native GABA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABA receptors implicated in multiple neurological diseases. Despite the profound importance of heteromeric GABA receptors in neuroscience and medicine, they have proven recalcitrant to structure determination. Here we present the structure of a tri-heteromeric α1β1γ2S GABA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding. Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating. Our work provides a pathway to structural studies of heteromeric GABA receptors and a framework for rational design of novel therapeutic agents.

PubMed: 30044221
DOI: 10.7554/eLife.39383

実験手法

ELECTRON MICROSCOPY (3.8 Å)