[日本語] English
万見- EMDB-53255: Dissociation-state-2 of 9-subunit CSN and SCF (SKP1-SKP2-CKS1) complex -
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データを開く
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基本情報
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| タイトル | Dissociation-state-2 of 9-subunit CSN and SCF (SKP1-SKP2-CKS1) complex | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | COP9 signalosome / Cullin-RING E3 LIGASE / LIGASE | |||||||||
| 機能・相同性 | 機能・相同性情報negative regulation of protein localization to nucleolus / negative regulation of protein neddylation / positive regulation of protein polyubiquitination / COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / regulation of IRE1-mediated unfolded protein response / Parkin-FBXW7-Cul1 ubiquitin ligase complex / exosomal secretion / GTPase inhibitor activity ...negative regulation of protein localization to nucleolus / negative regulation of protein neddylation / positive regulation of protein polyubiquitination / COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / regulation of IRE1-mediated unfolded protein response / Parkin-FBXW7-Cul1 ubiquitin ligase complex / exosomal secretion / GTPase inhibitor activity / cellular response to cell-matrix adhesion / deNEDDylase activity / F-box domain binding / Aberrant regulation of mitotic exit in cancer due to RB1 defects / protein deneddylation / regulation of protein neddylation / activation of NF-kappaB-inducing kinase activity / eukaryotic translation initiation factor 3 complex / PcG protein complex / COP9 signalosome / cullin-RING ubiquitin ligase complex / maintenance of protein location in nucleus / Cul7-RING ubiquitin ligase complex / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / cyclin-dependent protein serine/threonine kinase activator activity / protein neddylation / ubiquitin ligase activator 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 / metal-dependent deubiquitinase activity / RHOBTB1 GTPase cycle / regulation of JNK cascade / regulation of DNA damage response, signal transduction by p53 class mediator / inner cell mass cell proliferation / SCF ubiquitin ligase complex / positive regulation of intracellular estrogen receptor signaling pathway / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Prolactin receptor signaling / ubiquitin ligase complex scaffold activity / : / skeletal muscle cell differentiation / response to light stimulus / cullin family protein binding / protein monoubiquitination / protein K63-linked ubiquitination / positive regulation of double-strand break repair via homologous recombination / cyclin-dependent protein kinase holoenzyme complex / ubiquitin-like ligase-substrate adaptor activity / JNK cascade / Nuclear events stimulated by ALK signaling in cancer / protein K48-linked ubiquitination / translation initiation factor activity / post-translational protein modification / positive regulation of smooth muscle cell proliferation / intrinsic apoptotic signaling pathway / regulation of mitotic cell cycle / molecular function activator activity / animal organ morphogenesis / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / ubiquitin binding / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Vpu mediated degradation of CD4 / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of CRY and PER proteins / Activation of NF-kappaB in B cells / G1/S transition of mitotic cell cycle / Degradation of GLI1 by the proteasome / Iron uptake and transport / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Negative regulation of NOTCH4 signaling / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / Degradation of beta-catenin by the destruction complex / beta-catenin binding / NOTCH1 Intracellular Domain Regulates Transcription / DNA Damage Recognition in GG-NER / CLEC7A (Dectin-1) signaling / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / G2/M transition of mitotic cell cycle / SCF(Skp2)-mediated degradation of p27/p21 / FCERI mediated NF-kB activation / Formation of TC-NER Pre-Incision Complex / Interleukin-1 signaling / neuron differentiation / Orc1 removal from chromatin / metallopeptidase activity / protein polyubiquitination / Cyclin D associated events in G1 / Regulation of RUNX2 expression and activity / synaptic vesicle / cellular response to UV / cell junction / transcription corepressor activity / Regulation of PLK1 Activity at G2/M Transition / Downstream TCR signaling 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: 4.6 Å | |||||||||
データ登録者 | Ding S / Clapperton JA / Maeots ME / Enchev RI | |||||||||
| 資金援助 | 英国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2026タイトル: Structural basis of CSN-mediated SCF deneddylation. 著者: Shan Ding / Julie A Clapperton / Märt-Erik Mäeots / Simone Kunzelmann / Mohammed Shaaban / Radoslav I Enchev / ![]() 要旨: Cullin-RING ligases (CRLs) are the largest family of E3 ligases, with ubiquitination activity dynamically regulated by neddylation and deneddylation by the COP9 signalosome (CSN). CSN-mediated ...Cullin-RING ligases (CRLs) are the largest family of E3 ligases, with ubiquitination activity dynamically regulated by neddylation and deneddylation by the COP9 signalosome (CSN). CSN-mediated deneddylation not only deactivates CRLs but also enables substrate receptor exchange. Although CSN is a promising drug target, the structural basis underlying its catalytic mechanism remains unclear. Here, we use cryo-electron microscopy (cryo-EM) to uncover distinct functional states of CSN-CRL (SCF) complexes, capturing key intermediates of the deneddylation cycle. We visualise an autoinhibited docking state and a catalytic intermediate in which CSN5 Ins-1 loop, RBX1 RING and neddylated Cullin WHB domains are repositioned for isopeptide cleavage. We further resolve four dissociation intermediates that define the stepwise release of CSN from its product, with RBX1 RING stabilising key interactions. Additionally, our structures locate CSNAP within a CSN3-CSN8 groove. Together, our study provides a mechanistic model for CSN function and informs the rational design of CSN-targeted therapeutics. | |||||||||
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構造の表示
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ダウンロードとリンク
-EMDBアーカイブ
| マップデータ | emd_53255.map.gz | 111.3 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-53255-v30.xml emd-53255.xml | 36.5 KB 36.5 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_53255_fsc.xml | 11.3 KB | 表示 | FSCデータファイル |
| 画像 | emd_53255.png | 94.3 KB | ||
| Filedesc metadata | emd-53255.cif.gz | 9.5 KB | ||
| その他 | emd_53255_half_map_1.map.gz emd_53255_half_map_2.map.gz | 98.6 MB 98.5 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-53255 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-53255 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 9qo3MC ![]() 9qo0C ![]() 9qo1C ![]() 9qo2C ![]() 9qo4C ![]() 9qo5C ![]() 9qo6C M: このマップから作成された原子モデル 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
| 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 |
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マップ
| ファイル | ダウンロード / ファイル: emd_53255.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| 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: 1.08 Å | ||||||||||||||||||||||||||||||||||||
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| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #2
| ファイル | emd_53255_half_map_1.map | ||||||||||||
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| 投影像・断面図 |
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| 密度ヒストグラム |
-ハーフマップ: #1
| ファイル | emd_53255_half_map_2.map | ||||||||||||
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| 投影像・断面図 |
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| 密度ヒストグラム |
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試料の構成要素
+全体 : 9-subunit COP9 signalosome and SCFSkp2-Cks1 complex
+超分子 #1: 9-subunit COP9 signalosome and SCFSkp2-Cks1 complex
+超分子 #2: 9-subunit COP9 signalosome
+超分子 #3: SCF
+超分子 #4: Skp1-Skp2-Cks1
+超分子 #5: Cullin-1
+分子 #1: COP9 signalosome complex subunit 1
+分子 #2: COP9 signalosome complex subunit 3
+分子 #3: COP9 signalosome complex subunit 4
+分子 #4: COP9 signalosome complex subunit 5
+分子 #5: COP9 signalosome complex subunit 6
+分子 #6: COP9 signalosome complex subunit 7b
+分子 #7: COP9 signalosome complex subunit 8
+分子 #8: Cullin-1
+分子 #9: S-phase kinase-associated protein 1
+分子 #10: S-phase kinase-associated protein 2
+分子 #11: Cyclin-dependent kinases regulatory subunit 1
+分子 #12: COP9 signalosome complex subunit 2
+分子 #13: COP9 signalosome complex subunit 9
+分子 #14: ZINC ION
+分子 #15: INOSITOL HEXAKISPHOSPHATE
+分子 #16: water
-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 |
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試料調製
| 濃度 | 3.3 mg/mL |
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| 緩衝液 | pH: 7.5 / 詳細: 15 mM Hepes pH 7.5, 120 mM NaCl, 0.5 mM DTT |
| 凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
| 顕微鏡 | TFS KRIOS |
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| 撮影 | フィルム・検出器のモデル: FEI FALCON III (4k x 4k) 平均電子線量: 47.0 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: SPOT SCAN / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 5.0 µm / 最小 デフォーカス(公称値): 0.5 µm |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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コントローラー
万見について



キーワード
Homo sapiens (ヒト)
データ登録者
英国, 1件
引用



























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解析
FIELD EMISSION GUN

