+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6nt9 | |||||||||||||||||||||
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タイトル | Cryo-EM structure of the complex between human TBK1 and chicken STING | |||||||||||||||||||||
要素 |
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キーワード | IMMUNE SYSTEM (免疫系) / ER / kinase (キナーゼ) / adaptor | |||||||||||||||||||||
機能・相同性 | 機能・相同性情報 STING mediated induction of host immune responses / IRF3 mediated activation of type 1 IFN / STAT6-mediated induction of chemokines / positive regulation of xenophagy / serine/threonine protein kinase complex / proton channel activity / 2',3'-cyclic GMP-AMP binding / regulation of type I interferon production / dendritic cell proliferation / cyclic-di-GMP binding ...STING mediated induction of host immune responses / IRF3 mediated activation of type 1 IFN / STAT6-mediated induction of chemokines / positive regulation of xenophagy / serine/threonine protein kinase complex / proton channel activity / 2',3'-cyclic GMP-AMP binding / regulation of type I interferon production / dendritic cell proliferation / cyclic-di-GMP binding / cGAS/STING signaling pathway / IRF3-mediated induction of type I IFN / positive regulation of type I interferon-mediated signaling pathway / reticulophagy / Interleukin-37 signaling / TNFR1-induced proapoptotic signaling / TRAF6 mediated IRF7 activation / cytoplasmic pattern recognition receptor signaling pathway / type I interferon-mediated signaling pathway / autophagosome membrane / positive regulation of interferon-alpha production / antiviral innate immune response / positive regulation of macroautophagy / autophagosome assembly / positive regulation of type I interferon production / オートファゴソーム / canonical NF-kappaB signal transduction / positive regulation of autophagy / negative regulation of TORC1 signaling / TICAM1-dependent activation of IRF3/IRF7 / positive regulation of TORC1 signaling / Regulation of innate immune responses to cytosolic DNA / activation of innate immune response / positive regulation of interferon-beta production / endoplasmic reticulum-Golgi intermediate compartment membrane / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Negative regulators of DDX58/IFIH1 signaling / Neutrophil degranulation / Regulation of TNFR1 signaling / phosphoprotein binding / peptidyl-threonine phosphorylation / response to virus / DDX58/IFIH1-mediated induction of interferon-alpha/beta / SARS-CoV-1 activates/modulates innate immune responses / protein complex oligomerization / positive regulation of peptidyl-serine phosphorylation / TRAF3-dependent IRF activation pathway / cytoplasmic vesicle / defense response to virus / protein phosphatase binding / peptidyl-serine phosphorylation / positive regulation of canonical NF-kappaB signal transduction / Potential therapeutics for SARS / nucleic acid binding / non-specific serine/threonine protein kinase / protein kinase activity / defense response to Gram-positive bacterium / 炎症 / ゴルジ体 / negative regulation of gene expression / protein phosphorylation / 自然免疫系 / protein serine kinase activity / intracellular membrane-bounded organelle / protein serine/threonine kinase activity / endoplasmic reticulum membrane / SARS-CoV-2 activates/modulates innate and adaptive immune responses / perinuclear region of cytoplasm / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / 核質 / ATP binding / identical protein binding / 細胞質基質 / 細胞質 類似検索 - 分子機能 | |||||||||||||||||||||
生物種 | Homo sapiens (ヒト) Gallus gallus (ニワトリ) | |||||||||||||||||||||
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: 3.3 Å | |||||||||||||||||||||
データ登録者 | Shang, G. / Zhang, C. / Chen, Z.J. / Bai, X. / Zhang, X. | |||||||||||||||||||||
資金援助 | 米国, 6件
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引用 | ジャーナル: Nature / 年: 2019 タイトル: Structural basis of STING binding with and phosphorylation by TBK1. 著者: Conggang Zhang / Guijun Shang / Xiang Gui / Xuewu Zhang / Xiao-Chen Bai / Zhijian J Chen / 要旨: The invasion of mammalian cytoplasm by microbial DNA from infectious pathogens or by self DNA from the nucleus or mitochondria represents a danger signal that alerts the host immune system. Cyclic ...The invasion of mammalian cytoplasm by microbial DNA from infectious pathogens or by self DNA from the nucleus or mitochondria represents a danger signal that alerts the host immune system. Cyclic GMP-AMP synthase (cGAS) is a sensor of cytoplasmic DNA that activates the type-I interferon pathway. On binding to DNA, cGAS is activated to catalyse the synthesis of cyclic GMP-AMP (cGAMP) from GTP and ATP. cGAMP functions as a second messenger that binds to and activates stimulator of interferon genes (STING). STING then recruits and activates tank-binding kinase 1 (TBK1), which phosphorylates STING and the transcription factor IRF3 to induce type-I interferons and other cytokines. However, how cGAMP-bound STING activates TBK1 and IRF3 is not understood. Here we present the cryo-electron microscopy structure of human TBK1 in complex with cGAMP-bound, full-length chicken STING. The structure reveals that the C-terminal tail of STING adopts a β-strand-like conformation and inserts into a groove between the kinase domain of one TBK1 subunit and the scaffold and dimerization domain of the second subunit in the TBK1 dimer. In this binding mode, the phosphorylation site Ser366 in the STING tail cannot reach the kinase-domain active site of bound TBK1, which suggests that STING phosphorylation by TBK1 requires the oligomerization of both proteins. Mutational analyses validate the interaction mode between TBK1 and STING and support a model in which high-order oligomerization of STING and TBK1, induced by cGAMP, leads to STING phosphorylation by TBK1. | |||||||||||||||||||||
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 | 6nt9.cif.gz | 244.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6nt9.ent.gz | 184.5 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6nt9.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/nt/6nt9 ftp://data.pdbj.org/pub/pdb/validation_reports/nt/6nt9 | HTTPS FTP |
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-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
#1: タンパク質 | 分子量: 85316.695 Da / 分子数: 2 / 変異: D135N / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: TBK1, NAK / 発現宿主: Homo sapiens (ヒト) 参照: UniProt: Q9UHD2, non-specific serine/threonine protein kinase #2: タンパク質 | 分子量: 44207.070 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Gallus gallus (ニワトリ) / 遺伝子: TMEM173 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: A0A1D5P7Q9, UniProt: E1C7U0*PLUS |
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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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由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 8 | ||||||||||||||||||||||||
試料 | 濃度: 4.5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||
試料支持 | 詳細: unspecified | ||||||||||||||||||||||||
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 FIELDBright-field microscopy |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 48 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
電子光学装置 | エネルギーフィルター名称: GIF Quantum LS / エネルギーフィルタースリット幅: 20 eV |
画像スキャン | 動画フレーム数/画像: 30 |
-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: C2 (2回回転対称) | ||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 86276 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: AB INITIO MODEL / 空間: REAL | ||||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 4IM0 Accession code: 4IM0 / Source name: PDB / タイプ: experimental model |