+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6ni3 | |||||||||
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タイトル | B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin mega-complex | |||||||||
要素 |
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キーワード | SIGNALING PROTEIN/IMMUNE SYSTEM / GPCR / Gs protein / signaling transducer / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||
機能・相同性 | 機能・相同性情報 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 ...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 / negative regulation of smooth muscle contraction / positive regulation of lipophagy / negative regulation of multicellular organism growth / negative regulation of G protein-coupled receptor signaling pathway / response to psychosocial stress / endosome to lysosome transport / adrenergic receptor signaling pathway / diet induced thermogenesis / neuronal dense core vesicle / adenylate cyclase-activating adrenergic receptor signaling pathway / positive regulation of protein kinase A signaling / 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 / response to cold / peptidoglycan catabolic process / receptor-mediated endocytosis / 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 / 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 / Cargo recognition for clathrin-mediated endocytosis / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / lysozyme / lysozyme activity / GTPase binding / Clathrin-mediated endocytosis / retina development in camera-type eye / Ca2+ pathway / amyloid-beta binding / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / host cell cytoplasm / transcription by RNA polymerase II / cell population proliferation / positive regulation of MAPK cascade / Extra-nuclear estrogen signaling / early endosome / receptor complex / lysosome / cell surface receptor signaling pathway / endosome membrane 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) Enterobacteria phage RB59 (ファージ) Lama glama (ラマ) | |||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.8 Å | |||||||||
データ登録者 | Nguyen, A.H. / Thomsen, A.R.B. / Cahill, T.J. / des Georges, A. / Lefkowitz, R.J. | |||||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6ni3.cif.gz | 266 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6ni3.ent.gz | 200.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6ni3.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 6ni3_validation.pdf.gz | 904.1 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6ni3_full_validation.pdf.gz | 910.6 KB | 表示 | |
XML形式データ | 6ni3_validation.xml.gz | 33.9 KB | 表示 | |
CIF形式データ | 6ni3_validation.cif.gz | 51.3 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ni/6ni3 ftp://data.pdbj.org/pub/pdb/validation_reports/ni/6ni3 | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABG
#1: タンパク質 | 分子量: 44326.160 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAS, GNAS1, GSP / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P63092 |
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#2: タンパク質 | 分子量: 38534.062 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNB1 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P62873 |
#3: タンパク質 | 分子量: 7861.143 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNG2 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P59768 |
-タンパク質 / 抗体 / 非ポリマー , 3種, 3分子 RN
#4: タンパク質 | 分子量: 57630.762 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Enterobacteria phage RB59 (ファージ), (組換発現) Homo sapiens (ヒト) 遺伝子: e, RB59_126, ADRB2, ADRB2R, B2AR 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: A0A097J809, UniProt: P07550, lysozyme |
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#5: 抗体 | 分子量: 15140.742 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Lama glama (ラマ) / 発現宿主: Escherichia coli (大腸菌) |
#6: 化合物 | ChemComp-P0G / |
-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 |
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分子量 | 単位: MEGADALTONS / 実験値: NO | ||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.4 | ||||||||||||||||||||||||
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||
試料支持 | 詳細: unidentified | ||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 104 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||
対称性 | 点対称性: C1 (非対称) | |||||||||||||||
3次元再構成 | 解像度: 3.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 299893 / 対称性のタイプ: POINT |