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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: PDB / ID: 9m1h | |||||||||||||||||||||
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| タイトル | Cryo-EM structure of PGE2-EP1-Gq complex | |||||||||||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / GPCR / EP1 / PGE2 / Gq | |||||||||||||||||||||
| 機能・相同性 | 機能・相同性情報prostaglandin E receptor activity / Prostanoid ligand receptors / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / phospholipase C-activating serotonin receptor signaling pathway / PLC beta mediated events / regulation of platelet activation / entrainment of circadian clock / regulation of canonical Wnt signaling pathway ...prostaglandin E receptor activity / Prostanoid ligand receptors / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / phospholipase C-activating serotonin receptor signaling pathway / PLC beta mediated events / regulation of platelet activation / entrainment of circadian clock / regulation of canonical Wnt signaling pathway / glutamate receptor signaling pathway / phototransduction, visible light / PKA activation in glucagon signalling / developmental growth / hair follicle placode formation / photoreceptor outer segment / neuropeptide signaling pathway / D1 dopamine receptor binding / intracellular transport / postsynaptic cytosol / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / adenylate cyclase inhibitor activity / activation of adenylate cyclase activity / Hedgehog 'off' state / positive regulation of protein localization to cell cortex / T cell migration / adenylate cyclase-activating adrenergic receptor signaling pathway / Adenylate cyclase inhibitory pathway / enzyme regulator activity / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / cellular response to glucagon stimulus / regulation of insulin secretion / cellular response to forskolin / GTPase activator activity / regulation of mitotic spindle organization / adenylate cyclase activator activity / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / trans-Golgi network membrane / Regulation of insulin secretion / negative regulation of inflammatory response to antigenic stimulus / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / bone development / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / platelet aggregation / centriolar satellite / G-protein beta/gamma-subunit complex binding / cognition / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / blood coagulation / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / 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 / GDP binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / sensory perception of smell / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / 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 / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of cold-induced thermogenesis / retina development in camera-type eye 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: 2.55 Å | |||||||||||||||||||||
データ登録者 | Meng, X. / Xu, Y. / Xu, H.E. | |||||||||||||||||||||
| 資金援助 | 中国, 1件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2025タイトル: Structural insights into the activation of the human prostaglandin E receptor EP1 subtype by prostaglandin E. 著者: Xue Meng / Yang Li / Jiuyin Xu / Kai Wu / Wen Hu / Canrong Wu / H Eric Xu / Youwei Xu / ![]() 要旨: Prostaglandin E (PGE) mediates diverse physiological processes through four G protein-coupled receptor subtypes (EP1-EP4). While structures of EP2, EP3, and EP4 have been determined, the structural ...Prostaglandin E (PGE) mediates diverse physiological processes through four G protein-coupled receptor subtypes (EP1-EP4). While structures of EP2, EP3, and EP4 have been determined, the structural basis for PGE recognition and activation of the EP1 receptor subtype has remained elusive due to its inherent instability. Here, we present the cryoelectron microscopy structure of the human EP1 receptor in complex with PGE and heterotrimeric Gq protein at 2.55 Å resolution, completing the structural characterization of the EP receptor family. Our structure reveals a unique binding mode of PGE within EP1, involving key interactions with residues in the orthosteric pocket. Notably, we observe a less pronounced outward displacement of transmembrane helix 6 compared to other EP receptor subtypes, suggesting a distinct activation mechanism for EP1. Through extensive mutational analyses, we identify critical residues involved in PGE recognition, EP1 activation, and Gq protein coupling. By overcoming the challenges associated with the instability of EP1, our findings provide valuable insights into the subtype-specific activation mechanisms of EP receptors and lay the foundation for the development of more selective EP1-targeted therapeutics. | |||||||||||||||||||||
| 履歴 |
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構造の表示
| 構造ビューア | 分子: Molmil Jmol/JSmol |
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ダウンロードとリンク
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ダウンロード
| PDBx/mmCIF形式 | 9m1h.cif.gz | 172.5 KB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb9m1h.ent.gz | 132.1 KB | 表示 | PDB形式 |
| PDBx/mmJSON形式 | 9m1h.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
| 文書・要旨 | 9m1h_validation.pdf.gz | 1.3 MB | 表示 | wwPDB検証レポート |
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| 文書・詳細版 | 9m1h_full_validation.pdf.gz | 1.4 MB | 表示 | |
| XML形式データ | 9m1h_validation.xml.gz | 38.4 KB | 表示 | |
| CIF形式データ | 9m1h_validation.cif.gz | 56.1 KB | 表示 | |
| アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/m1/9m1h ftp://data.pdbj.org/pub/pdb/validation_reports/m1/9m1h | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 63571MC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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| 類似構造データ | 類似検索 - 機能・相同性 F&H 検索 |
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リンク
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集合体
| 登録構造単位 | ![]()
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要素
-タンパク質 , 1種, 1分子 A
| #1: タンパク質 | 分子量: 41847.230 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PTGER1 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P34995 |
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-Guanine nucleotide-binding protein ... , 3種, 3分子 BCG
| #2: タンパク質 | 分子量: 41724.383 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAI1, GNAS, GNAS1, GSP, GNAQ, GAQ / 発現宿主: Trichoplusia ni (イラクサキンウワバ)参照: UniProt: P63096, UniProt: P63092, UniProt: P50148, 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 |
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| #3: タンパク質 | 分子量: 37915.496 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNB1 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P62873 |
| #4: タンパク質 | 分子量: 7861.143 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNG2 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P59768 |
-非ポリマー , 2種, 2分子 


| #5: 化合物 | ChemComp-P2E / ( |
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| #6: 水 | ChemComp-HOH / |
-詳細
| 研究の焦点であるリガンドがあるか | N |
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| Has protein modification | N |
-実験情報
-実験
| 実験 | 手法: 電子顕微鏡法 |
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| 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 |
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試料調製
| 構成要素 | 名称: PGE2-EP1-Gq complex / タイプ: COMPLEX / Entity ID: #1-#4 / 由来: RECOMBINANT |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 由来(組換発現) | 生物種: Trichoplusia ni (イラクサキンウワバ) |
| 緩衝液 | pH: 7.5 |
| 試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
| 急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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| 顕微鏡 | モデル: TFS 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 FIELD / 最大 デフォーカス(公称値): 5000 nm / 最小 デフォーカス(公称値): 1200 nm |
| 撮影 | 電子線照射量: 30 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
| CTF補正 | タイプ: NONE |
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| 3次元再構成 | 解像度: 2.55 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 543885 / 対称性のタイプ: POINT |
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万見について




Homo sapiens (ヒト)
中国, 1件
引用
PDBj




























Trichoplusia ni (イラクサキンウワバ)
FIELD EMISSION GUN