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基本情報
登録情報 | データベース: EMDB / ID: EMD-30602 | |||||||||
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タイトル | Cryo-EM structure of the beclomethasone-bound adhesion receptor GPR97-Go complex | |||||||||
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![]() | GPCR / GPR97 / complex / adhesion G protein-coupled receptor / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() negative regulation of CREB transcription factor activity / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / vesicle docking involved in exocytosis / negative regulation of non-canonical NF-kappaB signal transduction / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / parallel fiber to Purkinje cell synapse / postsynaptic modulation of chemical synaptic transmission / negative regulation of insulin secretion ...negative regulation of CREB transcription factor activity / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / vesicle docking involved in exocytosis / negative regulation of non-canonical NF-kappaB signal transduction / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / parallel fiber to Purkinje cell synapse / postsynaptic modulation of chemical synaptic transmission / negative regulation of insulin secretion / specific granule membrane / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / muscle contraction / B cell differentiation / regulation of cell migration / GABA-ergic synapse / locomotory behavior / G protein-coupled receptor activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / 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) / presynaptic membrane / G protein activity / cell body / GTPase binding / retina development in camera-type eye / Ca2+ pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / fibroblast proliferation / G alpha (i) 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 / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / postsynaptic membrane / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / dendrite / Neutrophil degranulation / protein-containing complex binding / GTP binding / glutamatergic synapse / signal transduction / extracellular exosome / metal ion binding / membrane / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||
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手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.1 Å | |||||||||
![]() | Ping Y / Mao C | |||||||||
![]() | ![]() タイトル: Structures of the glucocorticoid-bound adhesion receptor GPR97-G complex. 著者: Yu-Qi Ping / Chunyou Mao / Peng Xiao / Ru-Jia Zhao / Yi Jiang / Zhao Yang / Wen-Tao An / Dan-Dan Shen / Fan Yang / Huibing Zhang / Changxiu Qu / Qingya Shen / Caiping Tian / Zi-Jian Li / ...著者: Yu-Qi Ping / Chunyou Mao / Peng Xiao / Ru-Jia Zhao / Yi Jiang / Zhao Yang / Wen-Tao An / Dan-Dan Shen / Fan Yang / Huibing Zhang / Changxiu Qu / Qingya Shen / Caiping Tian / Zi-Jian Li / Shaolong Li / Guang-Yu Wang / Xiaona Tao / Xin Wen / Ya-Ni Zhong / Jing Yang / Fan Yi / Xiao Yu / H Eric Xu / Yan Zhang / Jin-Peng Sun / ![]() 要旨: Adhesion G-protein-coupled receptors (GPCRs) are a major family of GPCRs, but limited knowledge of their ligand regulation or structure is available. Here we report that glucocorticoid stress ...Adhesion G-protein-coupled receptors (GPCRs) are a major family of GPCRs, but limited knowledge of their ligand regulation or structure is available. Here we report that glucocorticoid stress hormones activate adhesion G-protein-coupled receptor G3 (ADGRG3; also known as GPR97), a prototypical adhesion GPCR. The cryo-electron microscopy structures of GPR97-G complexes bound to the anti-inflammatory drug beclomethasone or the steroid hormone cortisol revealed that glucocorticoids bind to a pocket within the transmembrane domain. The steroidal core of glucocorticoids is packed against the 'toggle switch' residue W, which senses the binding of a ligand and induces activation of the receptor. Active GPR97 uses a quaternary core and HLY motif to fasten the seven-transmembrane bundle and to mediate G protein coupling. The cytoplasmic side of GPR97 has an open cavity, where all three intracellular loops interact with the G protein, contributing to the high basal activity of GRP97. Palmitoylation at the cytosolic tail of the G protein was found to be essential for efficient engagement with GPR97 but is not observed in other solved GPCR complex structures. Our work provides a structural basis for ligand binding to the seven-transmembrane domain of an adhesion GPCR and subsequent G protein coupling. | |||||||||
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構造の表示
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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マップデータ | ![]() | 17.8 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 18.4 KB 18.4 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 6.7 KB | 表示 | ![]() |
画像 | ![]() | 68.1 KB | ||
Filedesc metadata | ![]() | 6.7 KB | ||
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「今月の分子」の関連する項目 |
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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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試料の構成要素
+全体 : Beclomethasone-bound adhesion receptor GPR97-Go complex
+超分子 #1: Beclomethasone-bound adhesion receptor GPR97-Go complex
+超分子 #2: Adhesion G protein-coupled receptor G3; GPR97
+超分子 #3: Go
+分子 #1: Guanine nucleotide-binding protein G(o) subunit alpha
+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: Adhesion G protein-coupled receptor G3; GPR97
+分子 #5: PALMITIC ACID
+分子 #6: CHOLESTEROL HEMISUCCINATE
+分子 #7: (8~{S},9~{R},10~{S},11~{S},13~{S},14~{S},16~{S},17~{R})-9-chloran...
+分子 #8: CHOLESTEROL
-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
濃度 | 20 mg/mL |
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緩衝液 | pH: 7.5 |
グリッド | モデル: Quantifoil / 材質: GOLD / メッシュ: 200 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE |
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: 2707 / 平均電子線量: 62.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
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 |