+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8h33 | ||||||
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タイトル | Cryo-EM Structure of the KBTBD2-Cul3-Rbx1 tetrameric complex | ||||||
要素 |
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キーワード | LIGASE / complex | ||||||
機能・相同性 | 機能・相同性情報 liver morphogenesis / positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / POZ domain binding / nuclear protein quality control by the ubiquitin-proteasome system / regulation protein catabolic process at postsynapse / polar microtubule / anaphase-promoting complex-dependent catabolic process / COPII vesicle coating / stem cell division ...liver morphogenesis / positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / POZ domain binding / nuclear protein quality control by the ubiquitin-proteasome system / regulation protein catabolic process at postsynapse / polar microtubule / anaphase-promoting complex-dependent catabolic process / COPII vesicle coating / stem cell division / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / RHOBTB3 ATPase cycle / cullin-RING ubiquitin ligase complex / embryonic cleavage / cell projection organization / Cul7-RING ubiquitin ligase complex / positive regulation of mitotic metaphase/anaphase transition / 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 / NEDD8 ligase activity / Notch binding / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / RHOBTB1 GTPase cycle / fibroblast apoptotic process / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / negative regulation of Rho protein signal transduction / Cul2-RING ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / Cul4B-RING E3 ubiquitin ligase complex / negative regulation of type I interferon production / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / mitotic metaphase chromosome alignment / Cul3-RING ubiquitin ligase complex / stress fiber assembly / Prolactin receptor signaling / protein monoubiquitination / positive regulation of cytokinesis / cullin family protein binding / ubiquitin-like ligase-substrate adaptor activity / sperm flagellum / protein K48-linked ubiquitination / RHOBTB2 GTPase cycle / protein autoubiquitination / endoplasmic reticulum to Golgi vesicle-mediated transport / Nuclear events stimulated by ALK signaling in cancer / gastrulation / positive regulation of TORC1 signaling / T cell activation / phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of cellular response to insulin stimulus / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / cyclin binding / post-translational protein modification / positive regulation of protein ubiquitination / integrin-mediated signaling pathway / Degradation of DVL / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI1 by the proteasome / Negative regulation of NOTCH4 signaling / cellular response to amino acid stimulus / 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 / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / DNA Damage Recognition in GG-NER / protein destabilization / response to insulin / RING-type E3 ubiquitin transferase / negative regulation of canonical Wnt signaling pathway / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / lipid metabolic process / Formation of TC-NER Pre-Incision Complex / Dual Incision in GG-NER / Evasion by RSV of host interferon responses / NOTCH1 Intracellular Domain Regulates Transcription / mitotic spindle / Wnt signaling pathway / spindle pole / 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 / Dual incision in TC-NER / Interleukin-1 signaling / Orc1 removal from chromatin / Gap-filling DNA repair synthesis and ligation in TC-NER / Regulation of RAS by GAPs / protein polyubiquitination 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: 7.86 Å | ||||||
データ登録者 | Hu, Y. / Mao, Q. / Chen, Z. / Sun, L. | ||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2024 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. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8h33.cif.gz | 963.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8h33.ent.gz | 786.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8h33.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/h3/8h33 ftp://data.pdbj.org/pub/pdb/validation_reports/h3/8h33 | HTTPS FTP |
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-関連構造データ
関連構造データ | 34449MC 8gq6C 8h34C 8h35C 8h36C 8h37C 8h38C 8h3aC 8h3fC 8h3qC 8h3rC 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 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質 | 分子量: 71403.367 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q8IY47 #2: タンパク質 | 分子量: 13970.756 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: RBX1, RNF75, ROC1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P62877, RING-type E3 ubiquitin transferase, cullin-RING-type E3 NEDD8 transferase #3: タンパク質 | 分子量: 90105.469 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q13618 #4: 化合物 | ChemComp-ZN / 研究の焦点であるリガンドがあるか | Y | |
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-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 |
-試料調製
構成要素 | 名称: KBTBD2-Cul3-Rbx1 tetrameric complex / タイプ: COMPLEX / Entity ID: #1-#3 / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
緩衝液 | pH: 7.8 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-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): 2200 nm / 最小 デフォーカス(公称値): 1200 nm |
撮影 | 電子線照射量: 45 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||
3次元再構成 | 解像度: 7.86 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 50236 / 対称性のタイプ: POINT |