4MR7

Crystal structure of the extracellular domain of human GABA(B) receptor bound to the antagonist CGP54626

4MR7 の概要

• エントリーDOI: 10.2210/pdb4mr7/pdb
• 関連するPDBエントリー: 4MQE 4MQF 4MR8 4MR9 4MRM 4MS1 4MS3 4MS4
• 分子名称: Gamma-aminobutyric acid type B receptor subunit 1, Gamma-aminobutyric acid type B receptor subunit 2, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: heterodimeric protein complex, venus flytrap module, neurotransmitter receptor, signaling protein-antagonist complex, signaling protein/antagonist
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 99192.29

構造登録者

Geng, Y.,Bush, M.,Mosyak, L.,Wang, F.,Fan, Q.R. (登録日: 2013-09-17, 公開日: 2013-12-11, 最終更新日: 2024-11-20)

主引用文献

Geng, Y.,Bush, M.,Mosyak, L.,Wang, F.,Fan, Q.R.
Structural mechanism of ligand activation in human GABA(B) receptor.
Nature, 504:254-259, 2013

PubMed Abstract: Human GABA(B) (γ-aminobutyric acid class B) receptor is a G-protein-coupled receptor central to inhibitory neurotransmission in the brain. It functions as an obligatory heterodimer of the subunits GBR1 and GBR2. Here we present the crystal structures of a heterodimeric complex between the extracellular domains of GBR1 and GBR2 in the apo, agonist-bound and antagonist-bound forms. The apo and antagonist-bound structures represent the resting state of the receptor; the agonist-bound complex corresponds to the active state. Both subunits adopt an open conformation at rest, and only GBR1 closes on agonist-induced receptor activation. The agonists and antagonists are anchored in the interdomain crevice of GBR1 by an overlapping set of residues. An antagonist confines GBR1 to the open conformation of the inactive state, whereas an agonist induces its domain closure for activation. Our data reveal a unique activation mechanism for GABA(B) receptor that involves the formation of a novel heterodimer interface between subunits.

PubMed: 24305054
DOI: 10.1038/nature12725

実験手法

X-RAY DIFFRACTION (2.15 Å)