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	Structural basis of orientated asymmetry in a mGlu heterodimer.
ジャーナル・号・ページ	Nat Commun, Vol. 15, Issue 1, Page 10345, Year 2024
掲載日	2024年11月28日
著者	Weizhu Huang / Nan Jin / Jia Guo / Cangsong Shen / Chanjuan Xu / Kun Xi / Léo Bonhomme / Robert B Quast / Dan-Dan Shen / Jiao Qin / Yi-Ru Liu / Yuxuan Song / Yang Gao / Emmanuel Margeat / Philippe Rondard / Jean-Philippe Pin / Yan Zhang / Jianfeng Liu /
PubMed 要旨	The structural basis for the allosteric interactions within G protein-coupled receptors (GPCRs) heterodimers remains largely unknown. The metabotropic glutamate (mGlu) receptors are complex dimeric ...The structural basis for the allosteric interactions within G protein-coupled receptors (GPCRs) heterodimers remains largely unknown. The metabotropic glutamate (mGlu) receptors are complex dimeric GPCRs important for the fine tuning of many synapses. Heterodimeric mGlu receptors with specific allosteric properties have been identified in the brain. Here we report four cryo-electron microscopy structures of mGlu2-4 heterodimer in different states: an inactive state bound to antagonists, two intermediate states bound to either mGlu2 or mGlu4 agonist only and an active state bound to both glutamate and a mGlu4 positive allosteric modulator (PAM) in complex with Gi protein. In addition to revealing a unique PAM binding pocket among mGlu receptors, our data bring important information for the asymmetric activation of mGlu heterodimers. First, we show that agonist binding to a single subunit in the extracellular domain is not sufficient to stabilize an active dimer conformation. Single-molecule FRET data show that the monoliganded mGlu2-4 can be found in both intermediate states and an active one. Second, we provide a detailed view of the asymmetric interface in seven-transmembrane (7TM) domains and identified key residues within the mGlu2 7TM that limits its activation leaving mGlu4 as the only subunit activating G proteins.
リンク	Nat Commun / PubMed:39609406 / PubMed Central
手法	EM (単粒子)
解像度	3.13 - 5.95 Å
構造データ	37506 8wg9 EMDB-37506, PDB-8wg9: mGlu2-mGlu4 heterodimer bound mGlu4 agonist E7P 手法: EM (単粒子) / 解像度: 4.46 Å 37507 8wgb EMDB-37507, PDB-8wgb: mGlu2-4 heterodimer bound with Gi 手法: EM (単粒子) / 解像度: 3.7 Å 37508 8wgc EMDB-37508, PDB-8wgc: heterodimer of mGlu2 and mGlu4 bound with mGlu2 agonist LY379268 手法: EM (単粒子) / 解像度: 5.95 Å 37509 8wgd EMDB-37509, PDB-8wgd: mGlu2-4 inactive heterodimer 手法: EM (単粒子) / 解像度: 4.45 Å EMDB-61789: mGlu2-4 heterodimer bound with Gi 手法: EM (単粒子) / 解像度: 3.7 Å EMDB-61799: Cryo-EM structure of mGlu2-mGlu4 heterodimer bound mGlu4 agonist E7P 手法: EM (単粒子) / 解像度: 4.46 Å EMDB-61800: Cryo-EM structure of mGlu2-mGlu4 heterodimer bound mGlu4 agonist E7P 手法: EM (単粒子) / 解像度: 3.68 Å EMDB-61801: Cryo-EM structure of mGlu2-mGlu4 bound mGlu2 agonist LY379268 手法: EM (単粒子) / 解像度: 5.95 Å EMDB-61802: Cryo-EM structure of mGlu2-mGlu4 bound mGlu2 agonist LY379268 手法: EM (単粒子) / 解像度: 3.78 Å EMDB-61803: Cryo-EM structure of mGlu2-mGlu4 heterodimer bound with Gi 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-61804: Cryo-EM focused refined map of mGlu2-mGlu4 heterodimer bound with Gi 手法: EM (単粒子) / 解像度: 3.49 Å EMDB-61805: Cryo-EM focused refined map of mGlu2-mGlu4 heterodimer bound with Gi 手法: EM (単粒子) / 解像度: 3.75 Å EMDB-61806: Cryo-EM consensus map of inactive mGlu2-4 heterodimer 手法: EM (単粒子) / 解像度: 5.07 Å EMDB-61807: Cryo-EM focused refined map of inactive mGlu2-4 heterodimer 手法: EM (単粒子) / 解像度: 4.45 Å EMDB-61808: Cryo-EM focused refined map of inactive mGlu2-4 heterodimer 手法: EM (単粒子) / 解像度: 3.13 Å
化合物	ChemComp-E7P: (2S)-2-amino-4-phosphonobutanoic acid / L-AP4 / アゴニストYM ChemComp-GLU: GLUTAMIC ACID / グルタミン酸化合物画像なし ChemComp-W9R: Unknown entry 化合物画像なし ChemComp-W92: Unknown entry 化合物画像なし ChemComp-WAG: Unknown entry 化合物画像なし ChemComp-WA6*: Unknown entry
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN / GPCR