EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structures of human mGlu2 and mGlu7 homo- and heterodimers.
ジャーナル・号・ページ	Nature, Vol. 594, Issue 7864, Page 589-593, Year 2021
掲載日	2021年6月16日
著者	Juan Du / Dejian Wang / Hongcheng Fan / Chanjuan Xu / Linhua Tai / Shuling Lin / Shuo Han / Qiuxiang Tan / Xinwei Wang / Tuo Xu / Hui Zhang / Xiaojing Chu / Cuiying Yi / Peng Liu / Xiaomei Wang / Yu Zhou / Jean-Philippe Pin / Philippe Rondard / Hong Liu / Jianfeng Liu / Fei Sun / Beili Wu / Qiang Zhao /
PubMed 要旨	The metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system. These receptors probably exist as both ...The metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system. These receptors probably exist as both homo- and heterodimers that have unique pharmacological and functional properties. Here we report four cryo-electron microscopy structures of the human mGlu subtypes mGlu2 and mGlu7, including inactive mGlu2 and mGlu7 homodimers; mGlu2 homodimer bound to an agonist and a positive allosteric modulator; and inactive mGlu2-mGlu7 heterodimer. We observed a subtype-dependent dimerization mode for these mGlus, as a unique dimer interface that is mediated by helix IV (and that is important for limiting receptor activity) exists only in the inactive mGlu2 structure. The structures provide molecular details of the inter- and intra-subunit conformational changes that are required for receptor activation, which distinguish class C G-protein-coupled receptors from those in classes A and B. Furthermore, our structure and functional studies of the mGlu2-mGlu7 heterodimer suggest that the mGlu7 subunit has a dominant role in controlling dimeric association and G-protein activation in the heterodimer. These insights into mGlu homo- and heterodimers highlight the complex landscape of mGlu dimerization and activation.
リンク	Nature / PubMed:34135509
手法	EM (単粒子) / X線回折
解像度	2.5 - 4.0 Å
構造データ	31235 7epa EMDB-31235, PDB-7epa: Cryo-EM structure of inactive mGlu2 homodimer 手法: EM (単粒子) / 解像度: 3.6 Å 31236 7epb EMDB-31236, PDB-7epb: Cryo-EM structure of LY354740-bound mGlu2 homodimer 手法: EM (単粒子) / 解像度: 3.1 Å 31237 7epc EMDB-31237, PDB-7epc: Cryo-EM structure of inactive mGlu7 homodimer 手法: EM (単粒子) / 解像度: 4.0 Å 31238 7epd EMDB-31238, PDB-7epd: Cryo-EM structure of inactive mGlu2-7 heterodimer 手法: EM (単粒子) / 解像度: 3.9 Å PDB-7epe: Crystal structure of mGlu2 bound to NAM563 手法: X-RAY DIFFRACTION / 解像度: 2.5 Å PDB-7epf: Crystal structure of mGlu2 bound to NAM597 手法: X-RAY DIFFRACTION / 解像度: 2.7 Å
化合物	ChemComp-40F: (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid / LY-354740 ChemComp-FMN: FLAVIN MONONUCLEOTIDE / FMN ChemComp-J9R: 4-(1-methylpyrazol-4-yl)-7-[[(2~{S})-2-(trifluoromethyl)morpholin-4-yl]methyl]quinoline-2-carboxamide ChemComp-J9U: (8~{R})-4-[2,4-bis(fluoranyl)phenyl]-8-methyl-7-[(2-methylpyrazol-3-yl)methyl]-6,8-dihydro-5~{H}-1,7-naphthyridine-2-carboxamide
由来	homo sapiens (ヒト) lama glama (ラマ)
キーワード	MEMBRANE PROTEIN / cryo-EM structure / GPCR