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データを開く
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基本情報
| 登録情報 | データベース: PDB / ID: 7r4h | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| タイトル | phospho-STING binding to adaptor protein complex-1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
要素 |
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キーワード | IMMUNE SYSTEM / STING / innate immunity / TGN / AP-1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 機能・相同性 | 機能・相同性情報basolateral protein secretion / Lysosome Vesicle Biogenesis / endosome to melanosome transport / AP-1 adaptor complex / mitotic cleavage furrow ingression / trans-Golgi Network Vesicle Budding / platelet dense granule organization / Glycosphingolipid transport / melanosome assembly / regulation of receptor internalization ...basolateral protein secretion / Lysosome Vesicle Biogenesis / endosome to melanosome transport / AP-1 adaptor complex / mitotic cleavage furrow ingression / trans-Golgi Network Vesicle Budding / platelet dense granule organization / Glycosphingolipid transport / melanosome assembly / regulation of receptor internalization / STING complex / Intra-Golgi traffic / regulation of Arp2/3 complex-mediated actin nucleation / STAT6-mediated induction of chemokines / Golgi Associated Vesicle Biogenesis / Synthesis of PIPs at the Golgi membrane / protein localization to endoplasmic reticulum / clathrin adaptor activity / 2',3'-cyclic GMP-AMP binding / cyclic-di-GMP binding / MHC class II antigen presentation / STING mediated induction of host immune responses / serine/threonine protein kinase complex / Nef Mediated CD4 Down-regulation / positive regulation of type I interferon-mediated signaling pathway / IRF3-mediated induction of type I IFN / dendritic spine organization / cGAS/STING signaling pathway / long-term synaptic depression / determination of left/right symmetry / proton channel activity / clathrin-coated vesicle / pattern recognition receptor signaling pathway / reticulophagy / COPI-dependent Golgi-to-ER retrograde traffic / clathrin binding / Lysosome Vesicle Biogenesis / cytoplasmic pattern recognition receptor signaling pathway / Golgi Associated Vesicle Biogenesis / cellular response to exogenous dsRNA / Synthesis of PIPs at the plasma membrane / cell leading edge / protein complex oligomerization / autophagosome membrane / positive regulation of macroautophagy / intracellular copper ion homeostasis / autophagosome assembly / positive regulation of type I interferon production / protein targeting / positive regulation of DNA-binding transcription factor activity / cellular response to interferon-beta / COPI-mediated anterograde transport / vesicle-mediated transport / positive regulation of defense response to virus by host / signaling adaptor activity / clathrin-coated pit / Neutrophil degranulation / antiviral innate immune response / endoplasmic reticulum-Golgi intermediate compartment membrane / MHC class II antigen presentation / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / activation of innate immune response / Regulation of innate immune responses to cytosolic DNA / positive regulation of interferon-beta production / protein serine/threonine kinase binding / autophagosome / cytoplasmic vesicle membrane / secretory granule membrane / Nef mediated downregulation of MHC class I complex cell surface expression / sarcomere / trans-Golgi network membrane / small monomeric GTPase / intracellular protein transport / kidney development / trans-Golgi network / cellular response to virus / SARS-CoV-1 activates/modulates innate immune responses / synaptic vesicle / peroxisome / presynapse / heart development / regulation of inflammatory response / defense response to virus / DNA-binding transcription factor binding / RNA polymerase II-specific DNA-binding transcription factor binding / mitochondrial outer membrane / early endosome / neuron projection / endosome / postsynaptic density / cilium / ciliary basal body / protein domain specific binding / Golgi membrane / lysosomal membrane / innate immune response / focal adhesion / intracellular membrane-bounded organelle / GTPase activity / synapse 類似検索 - 分子機能 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 生物種 | Homo sapiens (ヒト)![]() | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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: 2.34 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
データ登録者 | Xu, P. / Ablasser, A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 資金援助 | European Union, 1件
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引用 | ジャーナル: Nature / 年: 2022タイトル: Clathrin-associated AP-1 controls termination of STING signalling. 著者: Ying Liu / Pengbiao Xu / Sophie Rivara / Chong Liu / Jonathan Ricci / Xuefeng Ren / James H Hurley / Andrea Ablasser / ![]() 要旨: Stimulator of interferon genes (STING) functions downstream of cyclic GMP-AMP synthase in DNA sensing or as a direct receptor for bacterial cyclic dinucleotides and small molecules to activate ...Stimulator of interferon genes (STING) functions downstream of cyclic GMP-AMP synthase in DNA sensing or as a direct receptor for bacterial cyclic dinucleotides and small molecules to activate immunity during infection, cancer and immunotherapy. Precise regulation of STING is essential to ensure balanced immune responses and prevent detrimental autoinflammation. After activation, STING, a transmembrane protein, traffics from the endoplasmic reticulum to the Golgi, where its phosphorylation by the protein kinase TBK1 enables signal transduction. The mechanism that ends STING signalling at the Golgi remains unknown. Here we show that adaptor protein complex 1 (AP-1) controls the termination of STING-dependent immune activation. We find that AP-1 sorts phosphorylated STING into clathrin-coated transport vesicles for delivery to the endolysosomal system, where STING is degraded. We identify a highly conserved dileucine motif in the cytosolic C-terminal tail (CTT) of STING that, together with TBK1-dependent CTT phosphorylation, dictates the AP-1 engagement of STING. A cryo-electron microscopy structure of AP-1 in complex with phosphorylated STING explains the enhanced recognition of TBK1-activated STING. We show that suppression of AP-1 exacerbates STING-induced immune responses. Our results reveal a structural mechanism of negative regulation of STING and establish that the initiation of signalling is inextricably associated with its termination to enable transient activation of immunity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 履歴 |
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構造の表示
| 構造ビューア | 分子: Molmil Jmol/JSmol |
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ダウンロードとリンク
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ダウンロード
| PDBx/mmCIF形式 | 7r4h.cif.gz | 414.7 KB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb7r4h.ent.gz | 329.1 KB | 表示 | PDB形式 |
| PDBx/mmJSON形式 | 7r4h.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 | 7r4h_validation.pdf.gz | 1.4 MB | 表示 | wwPDB検証レポート |
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| 文書・詳細版 | 7r4h_full_validation.pdf.gz | 1.4 MB | 表示 | |
| XML形式データ | 7r4h_validation.xml.gz | 66.6 KB | 表示 | |
| CIF形式データ | 7r4h_validation.cif.gz | 101.3 KB | 表示 | |
| アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/r4/7r4h ftp://data.pdbj.org/pub/pdb/validation_reports/r4/7r4h | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 14312MC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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| 類似構造データ | 類似検索 - 機能・相同性 F&H 検索 |
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リンク
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集合体
| 登録構造単位 | ![]()
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要素
-AP-1 complex subunit ... , 4種, 4分子 BGMS
| #1: タンパク質 | 分子量: 66008.422 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: AP1B1, ADTB1, BAM22, CLAPB2 / 発現宿主: ![]() |
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| #3: タンパク質 | 分子量: 67399.242 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
| #5: タンパク質 | 分子量: 48606.730 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
| #6: タンパク質 | 分子量: 18321.338 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: AP1S3 / 発現宿主: ![]() |
-タンパク質 / タンパク質・ペプチド , 2種, 3分子 CHL
| #2: タンパク質 | 分子量: 18936.600 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: ARF1 / 発現宿主: ![]() #4: タンパク質・ペプチド | | 分子量: 1065.068 Da / 分子数: 1 / 由来タイプ: 組換発現 / 詳細: phospho-STING tail / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: STING1, ERIS, MITA, STING, TMEM173 / 発現宿主: ![]() |
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-非ポリマー , 2種, 4分子 


| #7: 化合物 | | #8: 化合物 | |
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-詳細
| 研究の焦点であるリガンドがあるか | Y |
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| Has protein modification | Y |
-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 |
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試料調製
| 構成要素 | 名称: phospho-STING binding to adaptor protein complex-1 / タイプ: COMPLEX / Entity ID: #1-#6 / 由来: RECOMBINANT | |||||||||||||||||||||||||
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| 由来(天然) | 生物種: Homo sapiens (ヒト) | |||||||||||||||||||||||||
| 由来(組換発現) | 生物種: ![]() | |||||||||||||||||||||||||
| 緩衝液 | pH: 7.4 / 詳細: PBS buffer | |||||||||||||||||||||||||
| 緩衝液成分 |
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| 試料 | 濃度: 0.8 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | |||||||||||||||||||||||||
| 試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||
| 急速凍結 | 凍結剤: ETHANE |
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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 / 最大 デフォーカス(公称値): 1800 nm / 最小 デフォーカス(公称値): 800 nm |
| 撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
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解析
| ソフトウェア | 名称: PHENIX / バージョン: 1.20rc2_4400: / 分類: 精密化 | ||||||||||||||||||||||||
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| EMソフトウェア | 名称: PHENIX / カテゴリ: モデル精密化 | ||||||||||||||||||||||||
| CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3次元再構成 | 解像度: 2.34 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 322238 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
| 拘束条件 |
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万見について




Homo sapiens (ヒト)

引用


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gel filtration

