+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-3316 | |||||||||
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タイトル | Cryo-EM structure of CSN-N8-CRL4ADDB2 at 8.3 A resolution | |||||||||
マップデータ | Cryo-EM of the human CSN-N8-CRL4ADDB2 complex at 8.3 A. | |||||||||
試料 |
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キーワード | COP9 Signalosome / Cullin-RING ligases / Cryo-EM | |||||||||
機能・相同性 | 機能・相同性情報 Dual Incision in GG-NER / DNA Damage Recognition in GG-NER / Formation of Incision Complex in GG-NER / Neddylation / Prolactin receptor signaling / regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / COP9 signalosome assembly / Regulation of BACH1 activity / Recognition of DNA damage by PCNA-containing replication complex / DNA Damage Recognition in GG-NER ...Dual Incision in GG-NER / DNA Damage Recognition in GG-NER / Formation of Incision Complex in GG-NER / Neddylation / Prolactin receptor signaling / regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / COP9 signalosome assembly / Regulation of BACH1 activity / Recognition of DNA damage by PCNA-containing replication complex / DNA Damage Recognition in GG-NER / Formation of TC-NER Pre-Incision Complex / trophectodermal cell proliferation / Dual Incision in GG-NER / Dual incision in TC-NER / Formation of Incision Complex in GG-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / macrophage migration inhibitory factor binding / Regulation of RAS by GAPs / Regulation of RUNX2 expression and activity / Degradation of GLI1 by the proteasome / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Degradation of DVL / Orc1 removal from chromatin / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / regulation of IRE1-mediated unfolded protein response / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Hedgehog 'on' state / negative regulation of granulocyte differentiation / exosomal secretion / Degradation of beta-catenin by the destruction complex / deNEDDylase activity / GTPase inhibitor activity / eukaryotic initiation factor 4E binding / Interleukin-1 signaling / regulation of protein neddylation / protein deneddylation / anaphase-promoting complex / activation of NF-kappaB-inducing kinase activity / KEAP1-NFE2L2 pathway / eukaryotic translation initiation factor 3 complex / GLI3 is processed to GLI3R by the proteasome / Neddylation / cullin-RING-type E3 NEDD8 transferase / Antigen processing: Ubiquitination & Proteasome degradation / cullin-RING ubiquitin ligase complex / COP9 signalosome / positive regulation by virus of viral protein levels in host cell / regulation of DNA damage checkpoint / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / regulation of nucleotide-excision repair / spindle assembly involved in female meiosis / regulation of proteolysis / epigenetic programming in the zygotic pronuclei / VCB complex / Cul4-RING E3 ubiquitin ligase complex / positive regulation of protein autoubiquitination / UV-damage excision repair / protein neddylation / metal-dependent deubiquitinase activity / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素 / NEDD8 ligase activity / biological process involved in interaction with symbiont / RHOBTB1 GTPase cycle / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / ubiquitin-ubiquitin ligase activity / inner cell mass cell proliferation / regulation of mitotic cell cycle phase transition / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / WD40-repeat domain binding / Cul4A-RING E3 ubiquitin ligase complex / negative regulation of type I interferon production / ubiquitin ligase complex scaffold activity / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul4B-RING E3 ubiquitin ligase complex / Cul3-RING ubiquitin ligase complex / negative regulation of reproductive process / negative regulation of developmental process / skeletal muscle cell differentiation / protein monoubiquitination / TGF-beta receptor signaling activates SMADs / somatic stem cell population maintenance / site of DNA damage / viral release from host cell / hemopoiesis / cullin family protein binding / regulation of JNK cascade / ectopic germ cell programmed cell death / response to light stimulus / anatomical structure morphogenesis / positive regulation of G1/S transition of mitotic cell cycle / proteasomal protein catabolic process / positive regulation of viral genome replication / protein K48-linked ubiquitination / response to UV / ubiquitin ligase complex / JNK cascade / positive regulation of gluconeogenesis 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Danio rerio (ゼブラフィッシュ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 8.3 Å | |||||||||
データ登録者 | Cavadini S / Fischer ES / Bunker RD / Potenza A / Lingaraju GM / Goldie KN / Mohamed WI / Faty M / Petzold G / Beckwith REJ ...Cavadini S / Fischer ES / Bunker RD / Potenza A / Lingaraju GM / Goldie KN / Mohamed WI / Faty M / Petzold G / Beckwith REJ / Tichkule R / Hassiepen U / Abdulrahman W / Pantelic RS / Matsumoto S / Sugasawa K / Stahlberg H / Thoma NH | |||||||||
引用 | ジャーナル: Nature / 年: 2016 タイトル: Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome. 著者: Simone Cavadini / Eric S Fischer / Richard D Bunker / Alessandro Potenza / Gondichatnahalli M Lingaraju / Kenneth N Goldie / Weaam I Mohamed / Mahamadou Faty / Georg Petzold / Rohan E J ...著者: Simone Cavadini / Eric S Fischer / Richard D Bunker / Alessandro Potenza / Gondichatnahalli M Lingaraju / Kenneth N Goldie / Weaam I Mohamed / Mahamadou Faty / Georg Petzold / Rohan E J Beckwith / Ritesh B Tichkule / Ulrich Hassiepen / Wassim Abdulrahman / Radosav S Pantelic / Syota Matsumoto / Kaoru Sugasawa / Henning Stahlberg / Nicolas H Thomä / 要旨: The cullin-RING ubiquitin E3 ligase (CRL) family comprises over 200 members in humans. The COP9 signalosome complex (CSN) regulates CRLs by removing their ubiquitin-like activator NEDD8. The CUL4A- ...The cullin-RING ubiquitin E3 ligase (CRL) family comprises over 200 members in humans. The COP9 signalosome complex (CSN) regulates CRLs by removing their ubiquitin-like activator NEDD8. The CUL4A-RBX1-DDB1-DDB2 complex (CRL4A(DDB2)) monitors the genome for ultraviolet-light-induced DNA damage. CRL4A(DBB2) is inactive in the absence of damaged DNA and requires CSN to regulate the repair process. The structural basis of CSN binding to CRL4A(DDB2) and the principles of CSN activation are poorly understood. Here we present cryo-electron microscopy structures for CSN in complex with neddylated CRL4A ligases to 6.4 Å resolution. The CSN conformers defined by cryo-electron microscopy and a novel apo-CSN crystal structure indicate an induced-fit mechanism that drives CSN activation by neddylated CRLs. We find that CSN and a substrate cannot bind simultaneously to CRL4A, favouring a deneddylated, inactive state for substrate-free CRL4 complexes. These architectural and regulatory principles appear conserved across CRL families, allowing global regulation by CSN. | |||||||||
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_3316.map.gz | 7.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-3316-v30.xml emd-3316.xml | 19.9 KB 19.9 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_3316.png | 1.2 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-3316 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-3316 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_3316_validation.pdf.gz | 255.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_3316_full_validation.pdf.gz | 254.7 KB | 表示 | |
XML形式データ | emd_3316_validation.xml.gz | 5.3 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3316 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3316 | 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_3316.map.gz / 形式: CCP4 / 大きさ: 7.8 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Cryo-EM of the human CSN-N8-CRL4ADDB2 complex at 8.3 A. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 2.6 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 : Recombinant human CSN-N8-CRL4ADDB2 complex.
+超分子 #1000: Recombinant human CSN-N8-CRL4ADDB2 complex.
+分子 #1: COP9 signalosome subunit 1
+分子 #2: COP9 signalosome subunit 2
+分子 #3: COP9 signalosome subunit 3
+分子 #4: COP9 signalosome subunit 4
+分子 #5: COP9 signalosome subunit 5
+分子 #6: COP9 signalosome subunit 6
+分子 #7: COP9 signalosome subunit 7A
+分子 #8: COP9 signalosome subunit 8
+分子 #9: CUL4A
+分子 #10: DNA DAMAGE-BINDING PROTEIN 1
+分子 #11: E3 UBIQUITIN-PROTEIN LIGASE RBX1
+分子 #12: NEDD8
+分子 #13: DNA DAMAGE-BINDING PROTEIN 2
-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
濃度 | 0.05 mg/mL |
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緩衝液 | pH: 7.4 / 詳細: 50mM HEPES, 200mM NaCl, 0.25mM TCEP |
グリッド | 詳細: Quantifoil holey carbon grids (R2/2, Cu 400 mesh) coated with an additional thin amorphous carbon layer. |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 93 K / 装置: LEICA EM GP / 手法: Blot for 1.5 seconds before plunging |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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日付 | 2015年4月1日 |
撮影 | カテゴリ: CCD フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 実像数: 1427 詳細: Every image is the average of 38 frames recorded by the direct electron detector |
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 / Cs: 2.7 mm / 最大 デフォーカス(公称値): 6.0 µm / 最小 デフォーカス(公称値): 2.0 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
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: 8.3 Å / 解像度の算出法: OTHER / ソフトウェア - 名称: EMAN2, RELION / 使用した粒子像数: 16090 |
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-原子モデル構築 1
初期モデル | PDB ID: |
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精密化 | 空間: REAL / プロトコル: FLEXIBLE FIT |
-原子モデル構築 2
初期モデル | PDB ID: |
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精密化 | 空間: REAL / プロトコル: FLEXIBLE FIT |
-原子モデル構築 3
初期モデル | PDB ID: |
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精密化 | 空間: REAL / プロトコル: FLEXIBLE FIT |