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基本情報
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タイトル | Structure of GPR55 in complex with G13 and synthetic agonist ML184 | |||||||||
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![]() | G protein-coupled receptor / GPCR / lipid agonist / cholesterol / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() D5 dopamine receptor binding / Rho-activating G protein-coupled receptor signaling pathway / regulation of fibroblast migration / cannabinoid receptor activity / Class A/1 (Rhodopsin-like receptors) / regulation of small GTPase mediated signal transduction / NRAGE signals death through JNK / branching involved in blood vessel morphogenesis / positive regulation of Rho protein signal transduction / negative regulation of vascular associated smooth muscle cell migration ...D5 dopamine receptor binding / Rho-activating G protein-coupled receptor signaling pathway / regulation of fibroblast migration / cannabinoid receptor activity / Class A/1 (Rhodopsin-like receptors) / regulation of small GTPase mediated signal transduction / NRAGE signals death through JNK / branching involved in blood vessel morphogenesis / positive regulation of Rho protein signal transduction / negative regulation of vascular associated smooth muscle cell migration / negative regulation of osteoclast differentiation / negative regulation of vascular associated smooth muscle cell proliferation / CDC42 GTPase cycle / regulation of postsynapse assembly / Rho protein signal transduction / bone resorption / RAC1 GTPase cycle / bioluminescence / guanyl-nucleotide exchange factor activity / generation of precursor metabolites and energy / brush border membrane / G protein-coupled receptor activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / platelet activation / regulation of blood pressure / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / melanosome / 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 / regulation of cell shape / Thrombin signalling through proteinase activated receptors (PARs) / G protein activity / GTPase binding / positive regulation of cytosolic calcium ion concentration / Ca2+ pathway / retina development in camera-type eye / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / fibroblast proliferation / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / in utero embryonic development / Ras protein signal transduction / cell differentiation / Extra-nuclear estrogen signaling / cell population proliferation / positive regulation of ERK1 and ERK2 cascade / postsynapse / G protein-coupled receptor signaling pathway / lysosomal membrane / focal adhesion / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / metal ion binding / nucleus / membrane / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.51 Å | |||||||||
![]() | Claff T / Ebenhoch R / Weichert D | |||||||||
資金援助 | 1件
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![]() | ![]() タイトル: Structural basis for lipid-mediated activation of G protein-coupled receptor GPR55. 著者: Tobias Claff / Rebecca Ebenhoch / Jörg T Kley / Aniket Magarkar / Herbert Nar / Dietmar Weichert / ![]() 要旨: GPR55 is an orphan G protein-coupled receptor (GPCR) and represents a promising drug target for cancer, inflammation, and metabolic diseases. The endogenous activation of lipid GPCRs can be solely ...GPR55 is an orphan G protein-coupled receptor (GPCR) and represents a promising drug target for cancer, inflammation, and metabolic diseases. The endogenous activation of lipid GPCRs can be solely mediated by membrane components and different lipids have been proposed as endogenous activators of GPR55, such as cannabinoids and lysophosphatidylinositols. Here, we determine high-resolution cryo-electron microscopy structures of the activated GPR55 in complex with heterotrimeric G and two structurally diverse ligands: the putative endogenous agonist 1-palmitoyl-2-lysophosphatidylinositol (LPI) and the synthetic agonist ML184. These results reveal insights into ligand recognition at GPR55, G protein coupling and receptor activation. Notably, an orthosteric binding site opening towards the membrane is observed in both structures, enabling direct interaction of the agonists with membrane lipids. The structural observations are supported by mutagenesis and functional experiments employing G protein dissociation assays. These findings will be of importance for the structure-based development of drugs targeting GPR55. | |||||||||
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画像 | ![]() | 65.4 KB | ||
Filedesc metadata | ![]() | 7.2 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 9ge2MC ![]() 9ge3C C: 同じ文献を引用 ( M: このマップから作成された原子モデル |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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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: 0.829 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
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試料の構成要素
+全体 : Structure of GPR55 in complex with G13 and synthetic agonist ML184
+超分子 #1: Structure of GPR55 in complex with G13 and synthetic agonist ML184
+超分子 #2: Guanine nucleotide-binding proteins
+超分子 #3: Single-chain variable fragment ScFv16
+超分子 #4: G-protein coupled receptor 55 with a GFP tag
+分子 #1: Guanine nucleotide-binding protein subunit alpha-13
+分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #3: Single-chain variable fragment ScFv16
+分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #5: Green fluorescent protein,G-protein coupled receptor 55
+分子 #7: 3-[4-(2,3-dimethylphenyl)piperazin-1-yl]carbonyl-N,N-dimethyl-4-p...
+分子 #8: CHOLESTEROL
+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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![]() | 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 | FEI TITAN 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: 45.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: OTHER / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 3.0 µm / 最小 デフォーカス(公称値): 0.8 µm / 倍率(公称値): 105000 |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |