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データを開く
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基本情報
| 登録情報 | ![]() | |||||||||
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| タイトル | Cryo-EM structure of the PGD2-bound prostaglandin D2 receptor (DP1)-Gs complex | |||||||||
マップデータ | structure of the PGD2-bound prostaglandin D2 receptor (DP1)-Gs complex | |||||||||
試料 |
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キーワード | GPCR / DP1 / BW245C / prostaglandin D2 receptor / prostanoid DP receptor / PGD receptor / PTGDR / Gs protein / DP1-selective agonist / PGD2 / MEMBRANE PROTEIN | |||||||||
| 機能・相同性 | 機能・相同性情報prostaglandin J receptor activity / prostaglandin D receptor activity / Prostanoid ligand receptors / adenosine metabolic process / cellular response to prostaglandin D stimulus / male sex determination / sleep / mast cell degranulation / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway ...prostaglandin J receptor activity / prostaglandin D receptor activity / Prostanoid ligand receptors / adenosine metabolic process / cellular response to prostaglandin D stimulus / male sex determination / sleep / mast cell degranulation / 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 / 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 / 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 / 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 類似検索 - 分子機能 | |||||||||
| 生物種 | Homo sapiens (ヒト) / ![]() | |||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.68 Å | |||||||||
データ登録者 | Davoudinasab B / Cherezov V / Han GW / KIm D | |||||||||
| 資金援助 | 米国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2025タイトル: Structural insights into the mechanism of activation and inhibition of the prostaglandin D2 receptor 1. 著者: Behnaz Davoudinasab / Aleksey Raskovalov / Woojin Lee / Donggyun Kim / Heesoo Kim / Jordy Homing Lam / Gye Won Han / Vsevolod Katritch / Vadim Cherezov / ![]() 要旨: The prostaglandin D2 receptor 1 (DP1), a member of the prostanoid G protein-coupled receptor (GPCR) family, plays critical roles in allergic responses, sleep regulation, immune modulation, and ...The prostaglandin D2 receptor 1 (DP1), a member of the prostanoid G protein-coupled receptor (GPCR) family, plays critical roles in allergic responses, sleep regulation, immune modulation, and vasodilation. Here, we present five high-resolution cryo-electron microscopy (cryo-EM) structures of the human DP1 receptor, including an apo structure, two inactive state structures bound to two different inverse agonists developed by ONO Pharmaceutical, and two active state structures in complex with the G protein and bound to the endogenous agonist PGD2 and its selective derivative BW245C. Structural analysis, complemented by molecular dynamics simulations and site-directed mutagenesis, reveals key residues involved in ligand recognition and suggests a distinct activation mechanism for DP1, which lacks most of the conserved class A GPCR motifs. Notably, the unique residue K76 within the conserved sodium pocket acts as a major activation switch, while amphiphilic helix 8 adopts an unconventional orientation essential for receptor function. These findings offer valuable insights into the structure and function of prostanoid receptors and may facilitate the development of therapeutics targeting DP1. | |||||||||
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構造の表示
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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_47802.map.gz | 92 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-47802-v30.xml emd-47802.xml | 26.5 KB 26.5 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_47802_fsc.xml | 11.9 KB | 表示 | FSCデータファイル |
| 画像 | emd_47802.png | 51.4 KB | ||
| Filedesc metadata | emd-47802.cif.gz | 7.6 KB | ||
| その他 | emd_47802_half_map_1.map.gz emd_47802_half_map_2.map.gz | 164.9 MB 164.9 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-47802 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-47802 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 9e9sMC ![]() 9au0C ![]() 9ee5C ![]() 9ei5C ![]() 9ekhC ![]() 71658 ![]() 76159 ![]() 76160 M: このマップから作成された原子モデル 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
| 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_47802.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| 注釈 | structure of the PGD2-bound prostaglandin D2 receptor (DP1)-Gs complex | ||||||||||||||||||||||||||||||||||||
| 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: 0.84 Å | ||||||||||||||||||||||||||||||||||||
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| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
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-添付データ
-ハーフマップ: Half Map B
| ファイル | emd_47802_half_map_1.map | ||||||||||||
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| 注釈 | Half Map B | ||||||||||||
| 投影像・断面図 |
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| 密度ヒストグラム |
-ハーフマップ: Half Map A
| ファイル | emd_47802_half_map_2.map | ||||||||||||
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| 注釈 | Half Map A | ||||||||||||
| 投影像・断面図 |
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| 密度ヒストグラム |
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試料の構成要素
+全体 : PGD2-bound prostaglandin D2 receptor (DP1)-Gs protein-Nb35 complex
+超分子 #1: PGD2-bound prostaglandin D2 receptor (DP1)-Gs protein-Nb35 complex
+分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #4: Prostaglandin D2 receptor
+分子 #5: Nanobody35
+分子 #6: PROSTAGLANDIN D2
+分子 #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
+分子 #8: CHOLESTEROL HEMISUCCINATE
+分子 #9: water
-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
| 緩衝液 | pH: 7.5 |
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| 凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
| 顕微鏡 | TFS KRIOS |
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| 撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 65.0 e/Å2 |
| 電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
| 電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 1.0 µm |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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万見について




キーワード
Homo sapiens (ヒト)
データ登録者
米国, 1件
引用





































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Y (Row.)
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解析
FIELD EMISSION GUN


