+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-9375 | |||||||||
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タイトル | Stabilized beta-arrestin 1-V2T subcomplex of a GPCR-G protein-beta-arrestin mega-complex | |||||||||
マップデータ | Stabilized beta-arrestin 1-V2T subcomplex of a 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 renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / MAP2K and MAPK activation / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / Activation of SMO / Golgi Associated Vesicle Biogenesis / Lysosome Vesicle Biogenesis / AP-2 adaptor complex binding ...renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / MAP2K and MAPK activation / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / Activation of SMO / Golgi Associated Vesicle Biogenesis / Lysosome Vesicle Biogenesis / AP-2 adaptor complex binding / clathrin heavy chain binding / Ub-specific processing proteases / clathrin coat of coated pit / hemostasis / desensitization of G protein-coupled receptor signaling pathway / positive regulation of systemic arterial blood pressure / telencephalon development / Cargo recognition for clathrin-mediated endocytosis / inositol hexakisphosphate binding / Clathrin-mediated endocytosis / clathrin-dependent endocytosis / G protein-coupled receptor internalization / acetylcholine receptor binding / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of intracellular signal transduction / G alpha (s) signalling events / clathrin binding / negative regulation of Notch signaling pathway / small molecule binding / pseudopodium / phosphatidylinositol-3,4,5-trisphosphate binding / positive regulation of receptor internalization / positive regulation of vasoconstriction / endocytic vesicle / activation of adenylate cyclase activity / cellular response to hormone stimulus / visual perception / peptide binding / clathrin-coated endocytic vesicle membrane / response to cytokine / G protein-coupled receptor binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / receptor internalization / Vasopressin regulates renal water homeostasis via Aquaporins / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / protein transport / cytoplasmic vesicle / ubiquitin-dependent protein catabolic process / G alpha (s) signalling events / positive regulation of ERK1 and ERK2 cascade / endosome / molecular adaptor activity / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / positive regulation of cell population proliferation / positive regulation of gene expression / perinuclear region of cytoplasm / Golgi apparatus / signal transduction / endoplasmic reticulum / membrane / nucleus / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | Lama glama (ラマ) / Bos taurus (ウシ) / synthetic construct (人工物) / 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: 4.0 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_9375.map.gz | 32.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-9375-v30.xml emd-9375.xml | 18.3 KB 18.3 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_9375.png | 151.6 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-9375 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9375 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_9375_validation.pdf.gz | 396.1 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_9375_full_validation.pdf.gz | 395.7 KB | 表示 | |
XML形式データ | emd_9375_validation.xml.gz | 6 KB | 表示 | |
CIF形式データ | emd_9375_validation.cif.gz | 6.9 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9375 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9375 | 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_9375.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 | Stabilized beta-arrestin 1-V2T subcomplex of a GPCR-G protein-beta-arrestin mega-complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 : Stabilized beta-arrestin 1-V2T subcomplex of a GPCR-G protein-bet...
+超分子 #1: Stabilized beta-arrestin 1-V2T subcomplex of a GPCR-G protein-bet...
+超分子 #2: Nanobody 32
+超分子 #3: Beta-arrestin-1
+超分子 #4: Fab30
+超分子 #5: Vasopressin 2 Tail
+分子 #1: Nanobody 32
+分子 #2: Beta-arrestin-1
+分子 #3: Fab30 Heavy Chain
+分子 #4: Fab30 Light Chain
+分子 #5: Vasopressin V2 receptor
-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: 4.0 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: 230021 |
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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 |