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基本情報
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タイトル | Cryo-EM Structure of the KBTBD2-CRL3~N8(removed)-CSN complex | |||||||||
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![]() | ligase / complex | |||||||||
機能・相同性 | ![]() COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / liver morphogenesis / POZ domain binding / regulation of IRE1-mediated unfolded protein response / exosomal secretion / GTPase inhibitor activity ...COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / liver morphogenesis / POZ domain binding / regulation of IRE1-mediated unfolded protein response / exosomal secretion / GTPase inhibitor activity / deNEDDylase activity / nuclear protein quality control by the ubiquitin-proteasome system / protein deneddylation / regulation of protein neddylation / polar microtubule / eukaryotic translation initiation factor 3 complex / regulation protein catabolic process at postsynapse / COPII vesicle coating / anaphase-promoting complex-dependent catabolic process / activation of NF-kappaB-inducing kinase activity / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / RHOBTB3 ATPase cycle / COP9 signalosome / cullin-RING ubiquitin ligase complex / positive regulation of mitotic metaphase/anaphase transition / cell projection organization / embryonic cleavage / cellular response to chemical stress / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / positive regulation of protein autoubiquitination / protein neddylation / regulation of JNK cascade / Notch binding / 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 / fibroblast apoptotic process / RHOBTB1 GTPase cycle / negative regulation of response to oxidative stress / Cul5-RING ubiquitin ligase complex / regulation of DNA damage response, signal transduction by p53 class mediator / SCF ubiquitin ligase complex / inner cell mass cell proliferation / Cul2-RING ubiquitin ligase complex / ubiquitin-ubiquitin ligase activity / negative regulation of type I interferon production / Cul4A-RING E3 ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / stem cell division / mitotic metaphase chromosome alignment / Cul3-RING ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / stress fiber assembly / positive regulation of cytokinesis / negative regulation of mitophagy / negative regulation of Rho protein signal transduction / Prolactin receptor signaling / response to light stimulus / cullin family protein binding / skeletal muscle cell differentiation / sperm flagellum / protein monoubiquitination / endoplasmic reticulum to Golgi vesicle-mediated transport / ubiquitin-like ligase-substrate adaptor activity / RHOBTB2 GTPase cycle / protein K48-linked ubiquitination / protein autoubiquitination / Nuclear events stimulated by ALK signaling in cancer / positive regulation of DNA-binding transcription factor activity / Regulation of BACH1 activity / JNK cascade / gastrulation / positive regulation of protein ubiquitination / regulation of cellular response to insulin stimulus / translation initiation factor activity / positive regulation of TORC1 signaling / post-translational protein modification / intrinsic apoptotic signaling pathway / negative regulation of insulin receptor signaling pathway / cyclin binding / T cell activation / Degradation of DVL / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI1 by the proteasome / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / integrin-mediated signaling pathway / Negative regulation of NOTCH4 signaling / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / DNA Damage Recognition in GG-NER / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / cellular response to amino acid stimulus / Degradation of beta-catenin by the destruction complex / phosphatidylinositol 3-kinase/protein kinase B signal transduction 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 7.51 Å | |||||||||
![]() | Hu Y / Mao Q / Chen Z / Sun L | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Dynamic molecular architecture and substrate recruitment of cullin3-RING E3 ligase CRL3. 著者: Yuxia Hu / Zhao Zhang / Qiyu Mao / Xiang Zhang / Aihua Hao / Yu Xun / Yeda Wang / Lin Han / Wuqiang Zhan / Qianying Liu / Yue Yin / Chao Peng / Eva Marie Y Moresco / Zhenguo Chen / Bruce Beutler / Lei Sun / ![]() ![]() 要旨: Phosphatidylinositol 3-kinase α, a heterodimer of catalytic p110α and one of five regulatory subunits, mediates insulin- and insulin like growth factor-signaling and, frequently, oncogenesis. ...Phosphatidylinositol 3-kinase α, a heterodimer of catalytic p110α and one of five regulatory subunits, mediates insulin- and insulin like growth factor-signaling and, frequently, oncogenesis. Cellular levels of the regulatory p85α subunit are tightly controlled by regulated proteasomal degradation. In adipose tissue and growth plates, failure of K48-linked p85α ubiquitination causes diabetes, lipodystrophy and dwarfism in mice, as in humans with SHORT syndrome. Here we elucidated the structures of the key ubiquitin ligase complexes regulating p85α availability. Specificity is provided by the substrate receptor KBTBD2, which recruits p85α to the cullin3-RING E3 ubiquitin ligase (CRL3). CRL3 forms multimers, which disassemble into dimers upon substrate binding (CRL3-p85α) and/or neddylation by the activator NEDD8 (CRL3~N8), leading to p85α ubiquitination and degradation. Deactivation involves dissociation of NEDD8 mediated by the COP9 signalosome and displacement of KBTBD2 by the inhibitor CAND1. The hereby identified structural basis of p85α regulation opens the way to better understanding disturbances of glucose regulation, growth and cancer. | |||||||||
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構造の表示
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マップデータ | ![]() | 34.2 MB | ![]() | |
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画像 | ![]() | 99.3 KB | ||
Filedesc metadata | ![]() | 9.1 KB | ||
その他 | ![]() ![]() | 29.6 MB 29.6 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 658 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 657.6 KB | 表示 | |
XML形式データ | ![]() | 10.8 KB | 表示 | |
CIF形式データ | ![]() | 12.6 KB | 表示 | |
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-関連構造データ
関連構造データ | ![]() 8h3aMC ![]() 8gq6C ![]() 8h33C ![]() 8h34C ![]() 8h35C ![]() 8h36C ![]() 8h37C ![]() 8h38C ![]() 8h3fC ![]() 8h3qC ![]() 8h3rC 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 ![]() |
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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 | ![]() | ||||||||||||||||||||||||||||||||||||
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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: 2.088 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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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_34462_half_map_1.map | ||||||||||||
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_34462_half_map_2.map | ||||||||||||
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投影像・断面図 |
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試料の構成要素
+全体 : Cryo-EM Structure of the KBTBD2-CRL3~N8-CSN complex
+超分子 #1: Cryo-EM Structure of the KBTBD2-CRL3~N8-CSN complex
+超分子 #2: CSN
+超分子 #3: KBTBD2, Cullin-3, Rbx1
+分子 #1: COP9 signalosome complex subunit 5
+分子 #2: COP9 signalosome complex subunit 1
+分子 #3: COP9 signalosome complex subunit 2
+分子 #4: COP9 signalosome complex subunit 3
+分子 #5: COP9 signalosome complex subunit 4
+分子 #6: COP9 signalosome complex subunit 6
+分子 #7: COP9 signalosome complex subunit 7b
+分子 #8: COP9 signalosome complex subunit 8
+分子 #9: Kelch repeat and BTB domain-containing protein 2
+分子 #10: Cullin-3
+分子 #11: E3 ubiquitin-protein ligase RBX1
+分子 #12: 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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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.8 |
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凍結 | 凍結剤: ETHANE |
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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: SUPER-RESOLUTION / 平均電子線量: 53.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
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): 2.2 µm / 最小 デフォーカス(公称値): 1.2 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: 詳細: 6r7f |
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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: 7.51 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: RELION (ver. 3.0) / 使用した粒子像数: 55391 |
初期 角度割当 | タイプ: PROJECTION MATCHING |
最終 角度割当 | タイプ: PROJECTION MATCHING |