+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6n52 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Metabotropic Glutamate Receptor 5 Apo Form | |||||||||
要素 | Metabotropic glutamate receptor 5 | |||||||||
キーワード | MEMBRANE PROTEIN (膜タンパク質) / Cell Surface Receptor (細胞表面受容体) | |||||||||
機能・相同性 | 機能・相同性情報 A2A adenosine receptor binding / regulation of translational elongation / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential / trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / positive regulation of long-term neuronal synaptic plasticity / : / desensitization of G protein-coupled receptor signaling pathway / G protein-coupled glutamate receptor signaling pathway ...A2A adenosine receptor binding / regulation of translational elongation / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential / trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / positive regulation of long-term neuronal synaptic plasticity / : / desensitization of G protein-coupled receptor signaling pathway / G protein-coupled glutamate receptor signaling pathway / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / astrocyte projection / Class C/3 (Metabotropic glutamate/pheromone receptors) / protein kinase C-activating G protein-coupled receptor signaling pathway / glutamate receptor activity / Neurexins and neuroligins / protein tyrosine kinase activator activity / : / positive regulation of protein tyrosine kinase activity / regulation of synaptic transmission, glutamatergic / protein tyrosine kinase binding / dendritic shaft / locomotory behavior / 学習 / G protein-coupled receptor activity / postsynaptic density membrane / synapse organization / regulation of protein phosphorylation / Schaffer collateral - CA1 synapse / 認識 / cellular response to amyloid-beta / regulation of translation / chemical synaptic transmission / G alpha (q) signalling events / 樹状突起スパイン / positive regulation of MAPK cascade / learning or memory / glutamatergic synapse / regulation of DNA-templated transcription / identical protein binding / 細胞膜 / 細胞質 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4 Å | |||||||||
データ登録者 | Koehl, A. / Hu, H. / Feng, D. / Sun, B. / Weis, W.I. / Skiniotis, G.S. / Mathiesen, J.M. / Kobilka, B.K. | |||||||||
資金援助 | 米国, 2件
| |||||||||
引用 | ジャーナル: Nature / 年: 2019 タイトル: Structural insights into the activation of metabotropic glutamate receptors. 著者: Antoine Koehl / Hongli Hu / Dan Feng / Bingfa Sun / Yan Zhang / Michael J Robertson / Matthew Chu / Tong Sun Kobilka / Toon Laeremans / Jan Steyaert / Jeffrey Tarrasch / Somnath Dutta / ...著者: Antoine Koehl / Hongli Hu / Dan Feng / Bingfa Sun / Yan Zhang / Michael J Robertson / Matthew Chu / Tong Sun Kobilka / Toon Laeremans / Jan Steyaert / Jeffrey Tarrasch / Somnath Dutta / Rasmus Fonseca / William I Weis / Jesper M Mathiesen / Georgios Skiniotis / Brian K Kobilka / 要旨: Metabotropic glutamate receptors are family C G-protein-coupled receptors. They form obligate dimers and possess extracellular ligand-binding Venus flytrap domains, which are linked by cysteine-rich ...Metabotropic glutamate receptors are family C G-protein-coupled receptors. They form obligate dimers and possess extracellular ligand-binding Venus flytrap domains, which are linked by cysteine-rich domains to their 7-transmembrane domains. Spectroscopic studies show that signalling is a dynamic process, in which large-scale conformational changes underlie the transmission of signals from the extracellular Venus flytraps to the G protein-coupling domains-the 7-transmembrane domains-in the membrane. Here, using a combination of X-ray crystallography, cryo-electron microscopy and signalling studies, we present a structural framework for the activation mechanism of metabotropic glutamate receptor subtype 5. Our results show that agonist binding at the Venus flytraps leads to a compaction of the intersubunit dimer interface, thereby bringing the cysteine-rich domains into close proximity. Interactions between the cysteine-rich domains and the second extracellular loops of the receptor enable the rigid-body repositioning of the 7-transmembrane domains, which come into contact with each other to initiate signalling. | |||||||||
履歴 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6n52.cif.gz | 266.5 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb6n52.ent.gz | 208.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6n52.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/n5/6n52 ftp://data.pdbj.org/pub/pdb/validation_reports/n5/6n52 | HTTPS FTP |
---|
-関連構造データ
-リンク
-集合体
登録構造単位 |
|
---|---|
1 |
|
-要素
#1: タンパク質 | 分子量: 97677.945 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GRM5, GPRC1E, MGLUR5 / プラスミド: PVL1392 / 細胞株 (発現宿主): SF9 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P41594 #2: 糖 | ChemComp-NAG / |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Metabotropic Glutamate Receptor 5 in Nanodiscs / タイプ: COMPLEX / 詳細: Metabotropic Glutamate Receptor 5 in Nanodiscs / Entity ID: #1 / 由来: RECOMBINANT | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
分子量 | 値: 0.2 MDa / 実験値: NO | |||||||||||||||
由来(天然) | 生物種: Homo sapiens (ヒト) | |||||||||||||||
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) 株: Sf9 | |||||||||||||||
緩衝液 | pH: 7.5 詳細: 100mM NaCl, 20 mM HEPES pH 7.5, 5uM FFMTEB added as a negative allosteric modulator. | |||||||||||||||
緩衝液成分 |
| |||||||||||||||
試料 | 濃度: 7 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: This sample was mono disperse as assayed by gel filtration. | |||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 200 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 | |||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 293 K 詳細: Addition 0.0005% Amphipol A8-35was added to sample prior to apply to grid; 3.5ul sample was applied; blot for 1s before plunging |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy / 倍率(公称値): 130000 X / 倍率(補正後): 47169 X / Cs: 2.7 mm / C2レンズ絞り径: 50 µm |
撮影 | 電子線照射量: 50 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
EMソフトウェア |
| ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||
3次元再構成 | 解像度: 4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 123096 / 対称性のタイプ: POINT |