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データを開く
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基本情報
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| タイトル | Structure of the GPR88-Gi1 signaling complex bound to a synthetic ligand | |||||||||
マップデータ | Structure of the GPR88-Gi1 signaling complex | |||||||||
試料 |
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キーワード | GPR88 / signaling complex / cryo-EM / MEMBRANE PROTEIN | |||||||||
| 機能・相同性 | 機能・相同性情報motor learning / G protein-coupled photoreceptor activity / cellular response to light stimulus / beta2-adrenergic receptor activity / neuromuscular process controlling balance / ciliary membrane / cytoskeletal motor activity / phototransduction / neuronal action potential / adenylate cyclase inhibitor activity ...motor learning / G protein-coupled photoreceptor activity / cellular response to light stimulus / beta2-adrenergic receptor activity / neuromuscular process controlling balance / ciliary membrane / cytoskeletal motor activity / phototransduction / neuronal action potential / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / chemokine-mediated signaling pathway / Regulation of insulin secretion / neuropeptide signaling pathway / locomotory behavior / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / 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) / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / GDP binding / 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 alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / extracellular vesicle / sensory perception of taste / adenylate cyclase-activating G protein-coupled receptor signaling pathway / sperm principal piece / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / G protein activity / fibroblast proliferation / Ca2+ pathway / midbody / cell cortex / 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 / cilium / ciliary basal body / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / GTP binding / protein-containing complex binding / nucleolus 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: 2.4 Å | |||||||||
データ登録者 | Xu J / Chen G | |||||||||
| 資金援助 | 1件
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引用 | ジャーナル: Nat Commun / 年: 2022タイトル: Activation and allosteric regulation of the orphan GPR88-Gi1 signaling complex. 著者: Geng Chen / Jun Xu / Asuka Inoue / Maximilian F Schmidt / Chen Bai / Qiuyuan Lu / Peter Gmeiner / Zheng Liu / Yang Du / ![]() 要旨: GPR88 is an orphan class A G-protein-coupled receptor that is highly expressed in the striatum and regulates diverse brain and behavioral functions. Here we present cryo-EM structures of the human ...GPR88 is an orphan class A G-protein-coupled receptor that is highly expressed in the striatum and regulates diverse brain and behavioral functions. Here we present cryo-EM structures of the human GPR88-Gi1 signaling complex with or without a synthetic agonist (1R, 2R)-2-PCCA. We show that (1R, 2R)-2-PCCA is an allosteric modulator binding to a herein identified pocket formed by the cytoplasmic ends of transmembrane segments 5, 6, and the extreme C terminus of the α5 helix of Gi1. We also identify an electron density in the extracellular orthosteric site that may represent a putative endogenous ligand of GPR88. These structures, together with mutagenesis studies and an inactive state model obtained from metadynamics simulations, reveal a unique activation mechanism for GPR88 with a set of distinctive structure features and a water-mediated polar network. Overall, our results provide a structural framework for understanding the ligand binding, activation and signaling mechanism of GPR88, and will facilitate the innovative drug discovery for neuropsychiatric disorders and for deorphanization of this receptor. | |||||||||
| 履歴 |
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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_31164.map.gz | 64.7 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-31164-v30.xml emd-31164.xml | 17.2 KB 17.2 KB | 表示 表示 | EMDBヘッダ |
| 画像 | emd_31164.png | 137 KB | ||
| Filedesc metadata | emd-31164.cif.gz | 6.4 KB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-31164 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31164 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 7ejxMC ![]() 7wz4C 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_31164.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| 注釈 | Structure of the GPR88-Gi1 signaling 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: 0.83 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
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試料の構成要素
+全体 : GPR88-Gi1 signaling complex
+超分子 #1: GPR88-Gi1 signaling complex
+超分子 #2: GPR88-Gi1
+超分子 #3: scFv16
+分子 #1: Probable G-protein coupled receptor 88
+分子 #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
+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: scFv16
+分子 #6: (1R,2R)-N-[(2S,3S)-2-azanyl-3-methyl-pentyl]-N-[4-(4-propylphenyl...
+分子 #7: CHOLESTEROL
+分子 #8: 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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| 糖包埋 | 材質: vitreous ice |
| 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 BIOQUANTUM (6k x 4k) 平均電子線量: 56.0 e/Å2 |
| 電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
| 電子光学系 | 最大 デフォーカス(補正後): 2.0 µm / 最小 デフォーカス(補正後): 0.8 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm 最大 デフォーカス(公称値): 1.4000000000000001 µm 最小 デフォーカス(公称値): 1.0 µm / 倍率(公称値): 105000 |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
| 初期モデル | モデルのタイプ: INSILICO MODEL |
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| 最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 988958 |
| 初期 角度割当 | タイプ: RANDOM ASSIGNMENT |
| 最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
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万見について




キーワード
Homo sapiens (ヒト)
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FIELD EMISSION GUN
