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	Conformational diversity in class C GPCR positive allosteric modulation.
ジャーナル・号・ページ	Nat Commun, Vol. 16, Issue 1, Page 619, Year 2025
掲載日	2025年1月13日
著者	Giuseppe Cannone / Ludovic Berto / Fanny Malhaire / Gavin Ferguson / Aurelien Fouillen / Stéphanie Balor / Joan Font-Ingles / Amadeu Llebaria / Cyril Goudet / Abhay Kotecha / Vinothkumar K R / Guillaume Lebon /
PubMed 要旨	The metabotropic glutamate receptors (mGlus) are class C G protein-coupled receptors (GPCR) that form obligate dimers activated by the major excitatory neurotransmitter L-glutamate. The architecture ...The metabotropic glutamate receptors (mGlus) are class C G protein-coupled receptors (GPCR) that form obligate dimers activated by the major excitatory neurotransmitter L-glutamate. The architecture of mGlu receptor comprises an extracellular Venus-Fly Trap domain (VFT) connected to the transmembrane domain (7TM) through a Cysteine-Rich Domain (CRD). The binding of L-glutamate in the VFTs and subsequent conformational change results in the signal being transmitted to the 7TM inducing G protein binding and activation. The mGlu receptors signal transduction can be allosterically potentiated by positive allosteric modulators (PAMs) binding to the 7TMs, which are of therapeutic interest in various neurological disorders. Here, we report the cryoEM structures of metabotropic glutamate receptor 5 (mGlu) purified with three chemically and pharmacologically distinct PAMs. We find that the PAMs modulate the receptor equilibrium through their different binding modes, revealing how their interactions in the 7TMs impact the mGlu receptor conformational landscape and function. In addition, we identified a PAM-free but agonist-bound intermediate state that also reveals interactions mediated by intracellular loop 2. The activation of mGlu receptor is a multi-step process in which the binding of the PAMs in the 7TM modulates the equilibrium towards the active state.
リンク	Nat Commun / PubMed:39805839 / PubMed Central
手法	EM (単粒子)
解像度	3.0 - 4.1 Å
構造データ	37973 8x0b EMDB-37973, PDB-8x0b: Human FL Metabotropic glutamate receptor 5, mGlu5-5M with Quisqualate and VU0424465 手法: EM (単粒子) / 解像度: 3.1 Å 37974 8x0c EMDB-37974, PDB-8x0c: Human FL Metabotropic glutamate receptor 5, mGlu5-5M with quisqualate and VU0424465, conformer 1 手法: EM (単粒子) / 解像度: 3.2 Å 37975 8x0d EMDB-37975, PDB-8x0d: Human FL Metabotropic glutamate receptor 5, mGlu5-5M with quisqualate and VU0424465, conformer 2 手法: EM (単粒子) / 解像度: 3.5 Å 37976 8x0e EMDB-37976, PDB-8x0e: Human FL Metabotropic glutamate receptor 5, mGlu5-5M with agonist and PAM, W785A mutant 手法: EM (単粒子) / 解像度: 3.4 Å 37977 8x0f EMDB-37977, PDB-8x0f: Human FL Metabotropic glutamate receptor 5, mGlu5-5M with quisqualate and PAM VU29 手法: EM (単粒子) / 解像度: 3.3 Å 37978 8x0g EMDB-37978, PDB-8x0g: Human FL Metabotropic glutamate receptor 5, mGlu5-5M with quisqualate, Acc conformation (purified with PAM VU0409551 but not modelled) 手法: EM (単粒子) / 解像度: 3.0 Å 37979 8x0h EMDB-37979, PDB-8x0h: Human FL Metabotropic glutamate receptor 5, mGlu5-5M with quisqualate, Rcc conformation 手法: EM (単粒子) / 解像度: 4.1 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-QUS: (S)-2-AMINO-3-(3,5-DIOXO-[1,2,4]OXADIAZOLIDIN-2-YL)-PROPIONIC ACID / キスカル酸 / アゴニストYM 化合物画像なし ChemComp-XQT: Unknown entry ChemComp-HOH: WATER 化合物画像なし ChemComp-XRQ*: Unknown entry
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN / G-PROTEIN COUPLED RECEPTORS / SIGNAL TRANSDUCTION / METABOTROPIC GLUTAMATE RECEPTOR / Agonist / active state