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データを開く
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基本情報
| 登録情報 | データベース: EMDB / ID: EMD-30491 | |||||||||
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| タイトル | Cryo-EM structure of the Evatanepag-bound EP2-Gs complex | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | GPCR / EP2 / Complex / Evatanepag / MEMBRANE PROTEIN | |||||||||
| 機能・相同性 | 機能・相同性情報prostaglandin E receptor activity / Prostanoid ligand receptors / response to nematode / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / regulation of skeletal muscle contraction / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / intracellular transport ...prostaglandin E receptor activity / Prostanoid ligand receptors / response to nematode / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / regulation of skeletal muscle contraction / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / intracellular transport / D1 dopamine receptor binding / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / activation of adenylate cyclase activity / Hedgehog 'off' state / cellular response to acidic pH / adenylate cyclase-activating adrenergic receptor signaling pathway / response to progesterone / cellular response to glucagon stimulus / intracellular glucose homeostasis / positive regulation of insulin secretion involved in cellular response to glucose stimulus / adenylate cyclase activator activity / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / response to prostaglandin E / bone development / platelet aggregation / cognition / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / positive regulation of insulin secretion / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / sensory perception of smell / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / regulation of cell population proliferation / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G-protein beta-subunit binding / G alpha (12/13) signalling events / positive regulation of cold-induced thermogenesis / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / sensory perception of taste / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / positive regulation of cytosolic calcium ion concentration / retina development in camera-type eye / GTPase binding / G protein activity / fibroblast proliferation / Ca2+ pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / response to lipopolysaccharide / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / inflammatory response / lysosomal membrane / GTPase activity / synapse / GTP binding / protein-containing complex binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane 類似検索 - 分子機能 | |||||||||
| 生物種 | Homo sapiens (ヒト) / synthetic construct (人工物) | |||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.9 Å | |||||||||
データ登録者 | Qu C / Mao C | |||||||||
引用 | ジャーナル: Sci Adv / 年: 2021タイトル: Ligand recognition, unconventional activation, and G protein coupling of the prostaglandin E receptor EP2 subtype. 著者: Changxiu Qu / Chunyou Mao / Peng Xiao / Qingya Shen / Ya-Ni Zhong / Fan Yang / Dan-Dan Shen / Xiaona Tao / Huibing Zhang / Xu Yan / Ru-Jia Zhao / Junyan He / Ying Guan / Chao Zhang / Guihua ...著者: Changxiu Qu / Chunyou Mao / Peng Xiao / Qingya Shen / Ya-Ni Zhong / Fan Yang / Dan-Dan Shen / Xiaona Tao / Huibing Zhang / Xu Yan / Ru-Jia Zhao / Junyan He / Ying Guan / Chao Zhang / Guihua Hou / Peng-Ju Zhang / Guige Hou / Zijian Li / Xiao Yu / Ren-Jie Chai / You-Fei Guan / Jin-Peng Sun / Yan Zhang / ![]() 要旨: Selective modulation of the heterotrimeric G protein α S subunit-coupled prostaglandin E (PGE) receptor EP2 subtype is a promising therapeutic strategy for osteoporosis, ocular hypertension, ...Selective modulation of the heterotrimeric G protein α S subunit-coupled prostaglandin E (PGE) receptor EP2 subtype is a promising therapeutic strategy for osteoporosis, ocular hypertension, neurodegenerative diseases, and cardiovascular disorders. Here, we report the cryo-electron microscopy structure of the EP2-G complex with its endogenous agonist PGE and two synthesized agonists, taprenepag and evatanepag (CP-533536). These structures revealed distinct features of EP2 within the EP receptor family in terms of its unconventional receptor activation and G protein coupling mechanisms, including activation in the absence of a typical W "toggle switch" and coupling to G via helix 8. Moreover, inspection of the agonist-bound EP2 structures uncovered key motifs governing ligand selectivity. Our study provides important knowledge for agonist recognition and activation mechanisms of EP2 and will facilitate the rational design of drugs targeting the PGE signaling system. | |||||||||
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構造の表示
| ムービー |
ムービービューア |
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| 構造ビューア | EMマップ: SurfView Molmil Jmol/JSmol |
| 添付画像 |
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ダウンロードとリンク
-EMDBアーカイブ
| マップデータ | emd_30491.map.gz | 18 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-30491-v30.xml emd-30491.xml | 18.6 KB 18.6 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_30491_fsc.xml | 6.7 KB | 表示 | FSCデータファイル |
| 画像 | emd_30491.png | 68.5 KB | ||
| Filedesc metadata | emd-30491.cif.gz | 6.9 KB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-30491 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30491 | HTTPS FTP |
-関連構造データ
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リンク
| EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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| 「今月の分子」の関連する項目 |
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マップ
| ファイル | ダウンロード / ファイル: emd_30491.map.gz / 形式: CCP4 / 大きさ: 27 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ボクセルのサイズ | X=Y=Z: 1.014 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 密度 |
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| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
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試料の構成要素
+全体 : PGE2-bound EP2-Gs complex
+超分子 #1: PGE2-bound EP2-Gs complex
+超分子 #2: EP2
+超分子 #3: Nb35
+超分子 #4: Gs
+分子 #1: Prostaglandin E2 receptor EP2 subtype
+分子 #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #5: Nanobody-35
+分子 #6: 2-[3-[[(4-~{tert}-butylphenyl)methyl-pyridin-3-ylsulfonyl-amino]m...
-実験情報
-構造解析
| 手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
| 試料の集合状態 | particle |
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試料調製
| 濃度 | 5.0 mg/mL |
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| 緩衝液 | pH: 7.5 |
| グリッド | モデル: Quantifoil / 材質: GOLD / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY |
| 凍結 | 凍結剤: ETHANE / 装置: FEI VITROBOT MARK IV |
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電子顕微鏡法
| 顕微鏡 | FEI TITAN KRIOS |
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| 撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: COUNTING / 実像数: 2514 / 平均電子線量: 64.0 e/Å2 |
| 電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
| 電子光学系 | 倍率(補正後): 49310 / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 倍率(公称値): 29000 |
| 試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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コントローラー
万見について



キーワード
Homo sapiens (ヒト)
データ登録者
引用
UCSF Chimera




































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解析


