+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-4744 | |||||||||
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タイトル | Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome | |||||||||
マップデータ | None | |||||||||
試料 |
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キーワード | Cullin-Ring E3 Ligases (CRLs) COP9 signalosome (CSN) deneddylation VHL tumour suppressor substrate receptor / LIGASE | |||||||||
機能・相同性 | 機能・相同性情報 regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / COP9 signalosome assembly / trophectodermal cell proliferation / deNEDDylase activity / GTPase inhibitor activity / regulation of protein neddylation / protein deneddylation / activation of NF-kappaB-inducing kinase activity / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity ...regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / COP9 signalosome assembly / trophectodermal cell proliferation / deNEDDylase activity / GTPase inhibitor activity / regulation of protein neddylation / protein deneddylation / activation of NF-kappaB-inducing kinase activity / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / COP9 signalosome / cellular response to chemical stress / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / target-directed miRNA degradation / elongin complex / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / VCB complex / positive regulation of protein autoubiquitination / protein neddylation / NEDD8 ligase activity / RHOBTB1 GTPase cycle / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / ubiquitin-ubiquitin ligase activity / inner cell mass cell proliferation / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / Cul4A-RING E3 ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / negative regulation of type I interferon production / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin ligase complex scaffold activity / Cul3-RING ubiquitin ligase complex / Prolactin receptor signaling / skeletal muscle cell differentiation / protein monoubiquitination / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / cullin family protein binding / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / response to light stimulus / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / Formation of HIV elongation complex in the absence of HIV Tat / protein K48-linked ubiquitination / RNA Polymerase II Transcription Elongation / Nuclear events stimulated by ALK signaling in cancer / Formation of RNA Pol II elongation complex / JNK cascade / RNA Polymerase II Pre-transcription Events / positive regulation of TORC1 signaling / post-translational protein modification / intrinsic apoptotic signaling pathway / regulation of cellular response to insulin stimulus / Regulation of BACH1 activity / transcription corepressor binding / T cell activation / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / cellular response to amino acid stimulus / Degradation of DVL / transcription elongation by RNA polymerase II / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI1 by the proteasome / Negative regulation of NOTCH4 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / DNA Damage Recognition in GG-NER / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / RING-type E3 ubiquitin transferase / negative regulation of canonical Wnt signaling pathway / Inactivation of CSF3 (G-CSF) signaling / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / neuron differentiation / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Dual Incision in GG-NER / Evasion by RSV of host interferon responses / NOTCH1 Intracellular Domain Regulates Transcription / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Regulation of expression of SLITs and ROBOs / Formation of Incision Complex in GG-NER / Interleukin-1 signaling / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / Orc1 removal from chromatin / protein polyubiquitination / Regulation of RAS by GAPs / ubiquitin-protein transferase activity / G1/S transition of mitotic cell cycle / positive regulation of protein catabolic process / transcription corepressor activity 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: 6.5 Å | |||||||||
データ登録者 | Faull SV / Lau AMC | |||||||||
資金援助 | 英国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2019 タイトル: Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome. 著者: Sarah V Faull / Andy M C Lau / Chloe Martens / Zainab Ahdash / Kjetil Hansen / Hugo Yebenes / Carla Schmidt / Fabienne Beuron / Nora B Cronin / Edward P Morris / Argyris Politis / 要旨: Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. ...Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. Here we present structures of the neddylated and deneddylated CSN-CRL2 complexes by combining single-particle cryo-electron microscopy (cryo-EM) with chemical cross-linking mass spectrometry (XL-MS). These structures suggest a conserved mechanism of CSN activation, consisting of conformational clamping of the CRL2 substrate by CSN2/CSN4, release of the catalytic CSN5/CSN6 heterodimer and finally activation of the CSN5 deneddylation machinery. Using hydrogen-deuterium exchange (HDX)-MS we show that CRL2 activates CSN5/CSN6 in a neddylation-independent manner. The presence of NEDD8 is required to activate the CSN5 active site. Overall, by synergising cryo-EM with MS, we identify sensory regions of the CSN that mediate its stepwise activation and provide a framework for understanding the regulatory mechanism of other Cullin family members. | |||||||||
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_4744.map.gz | 37.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-4744-v30.xml emd-4744.xml | 22.5 KB 22.5 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_4744.png | 108.9 KB | ||
Filedesc metadata | emd-4744.cif.gz | 8.1 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-4744 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4744 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_4744_validation.pdf.gz | 357.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_4744_full_validation.pdf.gz | 357.1 KB | 表示 | |
XML形式データ | emd_4744_validation.xml.gz | 6.8 KB | 表示 | |
CIF形式データ | emd_4744_validation.cif.gz | 7.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4744 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4744 | 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_4744.map.gz / 形式: CCP4 / 大きさ: 103 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 1.06 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 : CNS (COP9 Signalosome) with CSN5/CSN6 the catalytic heterodimer c...
+超分子 #1: CNS (COP9 Signalosome) with CSN5/CSN6 the catalytic heterodimer c...
+分子 #1: COP9 signalosome complex subunit 1
+分子 #2: COP9 signalosome complex subunit 4
+分子 #3: COP9 signalosome complex subunit 8
+分子 #4: Elongin-B
+分子 #5: Elongin-C
+分子 #6: RBX1 E3 ubiquitin-protein ligase
+分子 #7: COP9 signalosome complex subunit 3
+分子 #8: CSN7B_HUMAN
+分子 #9: Cullin-2
+分子 #10: COP9 signalosome complex subunit 2
+分子 #11: ZINC ION
-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: 7.5 詳細: 15 mM HEPES pH 7.5 100 mM NaCl 0.5 mM DTT 1% Glycerol |
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凍結 | 凍結剤: ETHANE / 装置: FEI VITROBOT MARK IV |
-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 SUMMIT (4k x 4k) 検出モード: COUNTING / 平均電子線量: 45.0 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 / 最大 デフォーカス(公称値): 3.0 µm / 最小 デフォーカス(公称値): 1.8 µm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: NONE |
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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: 6.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 22471 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
-原子モデル構築 1
精密化 | プロトコル: FLEXIBLE FIT |
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得られたモデル | PDB-6r7n: |