+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-9377 | |||||||||
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タイトル | Structure of a GPCR-G protein-beta-arrestin mega-complex | |||||||||
マップデータ | GPCR-G protein-beta-arrestin mega-complex | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 MAP2K and MAPK activation / Activation of SMO / Golgi Associated Vesicle Biogenesis / Lysosome Vesicle Biogenesis / AP-2 adaptor complex binding / clathrin heavy chain binding / clathrin coat of coated pit / Ub-specific processing proteases / desensitization of G protein-coupled receptor signaling pathway / Cargo recognition for clathrin-mediated endocytosis ...MAP2K and MAPK activation / Activation of SMO / Golgi Associated Vesicle Biogenesis / Lysosome Vesicle Biogenesis / AP-2 adaptor complex binding / clathrin heavy chain binding / clathrin coat of coated pit / Ub-specific processing proteases / desensitization of G protein-coupled receptor signaling pathway / Cargo recognition for clathrin-mediated endocytosis / inositol hexakisphosphate binding / Clathrin-mediated endocytosis / clathrin-dependent endocytosis / G protein-coupled receptor internalization / acetylcholine receptor binding / beta2-adrenergic receptor activity / positive regulation of mini excitatory postsynaptic potential / positive regulation of cAMP-dependent protein kinase activity / positive regulation of AMPA receptor activity / positive regulation of autophagosome maturation / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / norepinephrine binding / heat generation / Adrenoceptors / activation of transmembrane receptor protein tyrosine kinase activity / Thrombin signalling through proteinase activated receptors (PARs) / negative regulation of smooth muscle contraction / G alpha (s) signalling events / positive regulation of lipophagy / negative regulation of multicellular organism growth / negative regulation of G protein-coupled receptor signaling pathway / clathrin binding / response to psychosocial stress / endosome to lysosome transport / adrenergic receptor signaling pathway / negative regulation of Notch signaling pathway / pseudopodium / diet induced thermogenesis / neuronal dense core vesicle / adenylate cyclase-activating adrenergic receptor signaling pathway / positive regulation of protein kinase A signaling / small molecule binding / positive regulation of receptor internalization / phosphatidylinositol-3,4,5-trisphosphate binding / adenylate cyclase binding / smooth muscle contraction / potassium channel regulator activity / bone resorption / positive regulation of bone mineralization / brown fat cell differentiation / regulation of sodium ion transport / viral release from host cell by cytolysis / visual perception / response to cold / peptidoglycan catabolic process / receptor-mediated endocytosis / G protein-coupled receptor binding / clathrin-coated endocytic vesicle membrane / positive regulation of protein serine/threonine kinase activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / receptor internalization / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to amyloid-beta / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / cell wall macromolecule catabolic process / extracellular vesicle / positive regulation of cold-induced thermogenesis 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: 4.84 Å | |||||||||
データ登録者 | Nguyen AH / Thomsen ARB / Cahill TJ / des Georges A / Lefkowitz RJ | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2019 タイトル: Structure of an endosomal signaling GPCR-G protein-β-arrestin megacomplex. 著者: Anthony H Nguyen / Alex R B Thomsen / Thomas J Cahill / Rick Huang / Li-Yin Huang / Tara Marcink / Oliver B Clarke / Søren Heissel / Ali Masoudi / Danya Ben-Hail / Fadi Samaan / Venkata P ...著者: Anthony H Nguyen / Alex R B Thomsen / Thomas J Cahill / Rick Huang / Li-Yin Huang / Tara Marcink / Oliver B Clarke / Søren Heissel / Ali Masoudi / Danya Ben-Hail / Fadi Samaan / Venkata P Dandey / Yong Zi Tan / Chuan Hong / Jacob P Mahoney / Sarah Triest / John Little / Xin Chen / Roger Sunahara / Jan Steyaert / Henrik Molina / Zhiheng Yu / Amedee des Georges / Robert J Lefkowitz / 要旨: Classically, G-protein-coupled receptors (GPCRs) are thought to activate G protein from the plasma membrane and are subsequently desensitized by β-arrestin (β-arr). However, some GPCRs continue to ...Classically, G-protein-coupled receptors (GPCRs) are thought to activate G protein from the plasma membrane and are subsequently desensitized by β-arrestin (β-arr). However, some GPCRs continue to signal through G protein from internalized compartments, mediated by a GPCR-G protein-β-arr 'megaplex'. Nevertheless, the molecular architecture of the megaplex remains unknown. Here, we present its cryo-electron microscopy structure, which shows simultaneous engagement of human G protein and bovine β-arr to the core and phosphorylated tail, respectively, of a single active human chimeric β-adrenergic receptor with the C-terminal tail of the arginine vasopressin type 2 receptor (βVR). All three components adopt their canonical active conformations, suggesting that a single megaplex GPCR is capable of simultaneously activating G protein and β-arr. Our findings provide a structural basis for GPCR-mediated sustained internalized G protein signaling. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_9377.map.gz | 49.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-9377-v30.xml emd-9377.xml | 10.7 KB 10.7 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_9377.png | 53.8 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-9377 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9377 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_9377_validation.pdf.gz | 79.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_9377_full_validation.pdf.gz | 78.4 KB | 表示 | |
XML形式データ | emd_9377_validation.xml.gz | 495 B | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9377 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9377 | HTTPS FTP |
-関連構造データ
-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 |
-マップ
ファイル | ダウンロード / ファイル: emd_9377.map.gz / 形式: CCP4 / 大きさ: 52.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | GPCR-G protein-beta-arrestin mega-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: 1.04 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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-添付データ
-試料の構成要素
-全体 : GPCR-G protein-beta-arrestin mega-complex
全体 | 名称: GPCR-G protein-beta-arrestin mega-complex |
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要素 |
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-超分子 #1: GPCR-G protein-beta-arrestin mega-complex
超分子 | 名称: GPCR-G protein-beta-arrestin mega-complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
-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 |
-試料調製
緩衝液 | pH: 7.4 |
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グリッド | 詳細: unidentified |
凍結 | 凍結剤: ETHANE |
-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 QUANTUM (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均電子線量: 104.0 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 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 4.84 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: cryoSPARC / 使用した粒子像数: 317529 |
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初期 角度割当 | タイプ: OTHER / ソフトウェア - 名称: cryoSPARC |
最終 角度割当 | タイプ: OTHER / ソフトウェア - 名称: cryoSPARC |