+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7b5n | |||||||||
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タイトル | Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: NEDD8-CUL1-RBX1-UBE2L3~Ub~ARIH1. | |||||||||
要素 |
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キーワード | LIGASE (リガーゼ) / ubiquitin (ユビキチン) / ubiquitin ligase (ユビキチンリガーゼ) / E3 ligase (ユビキチンリガーゼ) / F-box protein (Fボックスタンパク質) / RBR ligase / Cullin-RING-Ligase / CRL / SCF / NEDD8 / Post-translational modification (翻訳後修飾) / ubiquitylation (ユビキチン) | |||||||||
機能・相同性 | 機能・相同性情報 PKR/eIFalpha signaling / ubiquitin-like protein transferase activity / レビー小体 / Parkin-FBXW7-Cul1 ubiquitin ligase complex / RBR-type E3 ubiquitin transferase / cell cycle phase transition / ubiquitin-protein transferase activator activity / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity ...PKR/eIFalpha signaling / ubiquitin-like protein transferase activity / レビー小体 / Parkin-FBXW7-Cul1 ubiquitin ligase complex / RBR-type E3 ubiquitin transferase / cell cycle phase transition / ubiquitin-protein transferase activator activity / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / regulation of proteolysis / protein K11-linked ubiquitination / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / positive regulation of protein autoubiquitination / protein neddylation / ubiquitin conjugating enzyme binding / cellular response to glucocorticoid stimulus / positive regulation of ubiquitin-protein transferase activity / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin-ubiquitin ligase activity / positive regulation of protein targeting to mitochondrion / Cul4A-RING E3 ubiquitin ligase complex / ユビキチン結合酵素 / Cul2-RING ubiquitin ligase complex / SCF複合体 / negative regulation of type I interferon production / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / Cul3-RING ubiquitin ligase complex / cellular response to steroid hormone stimulus / Prolactin receptor signaling / protein monoubiquitination / ubiquitin conjugating enzyme activity / TGF-beta receptor signaling activates SMADs / cullin family protein binding / protein K48-linked ubiquitination / anatomical structure morphogenesis / カハール体 / Nuclear events stimulated by ALK signaling in cancer / ubiquitin ligase complex / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / グリコーゲン合成 / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Constitutive Signaling by NOTCH1 HD Domain Mutants / Endosomal Sorting Complex Required For Transport (ESCRT) / NOTCH2 Activation and Transmission of Signal to the Nucleus / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / positive regulation of TORC1 signaling / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Pexophagy / InlA-mediated entry of Listeria monocytogenes into host cells / Regulation of innate immune responses to cytosolic DNA / VLDLR internalisation and degradation / Downregulation of ERBB2:ERBB3 signaling / NRIF signals cell death from the nucleus / Activated NOTCH1 Transmits Signal to the Nucleus / NF-kB is activated and signals survival / Regulation of PTEN localization / Regulation of BACH1 activity / Translesion synthesis by REV1 / T細胞 / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / post-translational protein modification / Translesion synthesis by POLK / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / intrinsic apoptotic signaling pathway / Gap-filling DNA repair synthesis and ligation in GG-NER / Downregulation of TGF-beta receptor signaling / Translesion synthesis by POLI / Josephin domain DUBs / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Regulation of activated PAK-2p34 by proteasome mediated degradation / InlB-mediated entry of Listeria monocytogenes into host cell / IKK complex recruitment mediated by RIP1 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: 3.6 Å | |||||||||
データ登録者 | Horn-Ghetko, D. / Prabu, J.R. / Schulman, B.A. | |||||||||
資金援助 | ドイツ, 2件
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引用 | ジャーナル: Nature / 年: 2021 タイトル: Ubiquitin ligation to F-box protein targets by SCF-RBR E3-E3 super-assembly. 著者: Daniel Horn-Ghetko / David T Krist / J Rajan Prabu / Kheewoong Baek / Monique P C Mulder / Maren Klügel / Daniel C Scott / Huib Ovaa / Gary Kleiger / Brenda A Schulman / 要旨: E3 ligases are typically classified by hallmark domains such as RING and RBR, which are thought to specify unique catalytic mechanisms of ubiquitin transfer to recruited substrates. However, rather ...E3 ligases are typically classified by hallmark domains such as RING and RBR, which are thought to specify unique catalytic mechanisms of ubiquitin transfer to recruited substrates. However, rather than functioning individually, many neddylated cullin-RING E3 ligases (CRLs) and RBR-type E3 ligases in the ARIH family-which together account for nearly half of all ubiquitin ligases in humans-form E3-E3 super-assemblies. Here, by studying CRLs in the SKP1-CUL1-F-box (SCF) family, we show how neddylated SCF ligases and ARIH1 (an RBR-type E3 ligase) co-evolved to ubiquitylate diverse substrates presented on various F-box proteins. We developed activity-based chemical probes that enabled cryo-electron microscopy visualization of steps in E3-E3 ubiquitylation, initiating with ubiquitin linked to the E2 enzyme UBE2L3, then transferred to the catalytic cysteine of ARIH1, and culminating in ubiquitin linkage to a substrate bound to the SCF E3 ligase. The E3-E3 mechanism places the ubiquitin-linked active site of ARIH1 adjacent to substrates bound to F-box proteins (for example, substrates with folded structures or limited length) that are incompatible with previously described conventional RING E3-only mechanisms. The versatile E3-E3 super-assembly may therefore underlie widespread ubiquitylation. | |||||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7b5n.cif.gz | 237.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7b5n.ent.gz | 189.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7b5n.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/b5/7b5n ftp://data.pdbj.org/pub/pdb/validation_reports/b5/7b5n | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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-要素
-タンパク質 , 4種, 4分子 CUND
#1: タンパク質 | 分子量: 89800.367 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CUL1 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: Q13616 |
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#3: タンパク質 | 分子量: 8519.778 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: UBC / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P0CG48 |
#4: タンパク質 | 分子量: 9086.562 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: NEDD8 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: Q15843 |
#6: タンパク質 | 分子量: 17825.459 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: UBE2L3, UBCE7, UBCH7 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P68036, ユビキチン結合酵素 |
-E3 ubiquitin-protein ligase ... , 2種, 2分子 HR
#2: タンパク質 | 分子量: 64197.777 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: ARIH1, ARI, MOP6, UBCH7BP, HUSSY-27 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: Q9Y4X5, RBR-type E3 ubiquitin transferase |
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#5: タンパク質 | 分子量: 12289.977 Da / 分子数: 1 / 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: Trichoplusia ni (イラクサキンウワバ) 参照: UniProt: P62877, RING-type E3 ubiquitin transferase, cullin-RING-type E3 NEDD8 transferase |
-非ポリマー , 2種, 10分子
#7: 化合物 | ChemComp-ZN / #8: 化合物 | ChemComp-SY8 / | |
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-詳細
研究の焦点であるリガンドがあるか | N |
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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 |
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分子量 | 値: 0.30 MDa | ||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) |
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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 FIELDBright-field microscopy |
撮影 | 電子線照射量: 70 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.18.2_3874: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 623409 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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