+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7b5s | |||||||||
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タイトル | Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: CUL1-RBX1-ARIH1 Ariadne. Transition State 1 | |||||||||
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 / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex ...PKR/eIFalpha signaling / ubiquitin-like protein transferase activity / レビー小体 / Parkin-FBXW7-Cul1 ubiquitin ligase complex / RBR-type E3 ubiquitin transferase / 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 / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / positive regulation of protein autoubiquitination / protein neddylation / ubiquitin conjugating enzyme binding / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF複合体 / Cul2-RING ubiquitin ligase complex / negative regulation of type I interferon production / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / Nuclear events stimulated by ALK signaling in cancer / protein K48-linked ubiquitination / カハール体 / ubiquitin ligase complex / positive regulation of TORC1 signaling / T細胞 / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / intrinsic apoptotic signaling pathway / post-translational protein modification / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Degradation of DVL / Dectin-1 mediated noncanonical NF-kB signaling / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Negative regulation of NOTCH4 signaling / animal organ morphogenesis / Iron uptake and transport / cellular response to amino acid stimulus / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / 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 / RING-type E3 ubiquitin transferase / PKR-mediated signaling / Degradation of beta-catenin by the destruction complex / negative regulation of canonical Wnt signaling pathway / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / G1/S transition of mitotic cell cycle / Dual Incision in GG-NER / NOTCH1 Intracellular Domain Regulates Transcription / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / ISG15 antiviral mechanism / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / 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 / FCERI mediated NF-kB activation / Interleukin-1 signaling / Orc1 removal from chromatin / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / Regulation of RAS by GAPs / protein polyubiquitination / positive regulation of protein catabolic process / ubiquitin-protein transferase activity / Regulation of RUNX2 expression and activity / Cyclin D associated events in G1 / cellular response to UV / KEAP1-NFE2L2 pathway / Regulation of PLK1 Activity at G2/M Transition / ubiquitin protein ligase activity / 分裂促進因子活性化タンパク質キナーゼ / Circadian Clock / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / Downstream TCR signaling / protein-macromolecule adaptor activity / Neddylation / ubiquitin-dependent protein catabolic process / 精子形成 / proteasome-mediated ubiquitin-dependent protein catabolic process / positive regulation of canonical NF-kappaB signal transduction 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 | 7b5s.cif.gz | 191.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7b5s.ent.gz | 144.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7b5s.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/b5/7b5s ftp://data.pdbj.org/pub/pdb/validation_reports/b5/7b5s | 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
#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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#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 | ||
#3: 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 | ||
#4: 化合物 | ChemComp-ZN / 研究の焦点であるリガンドがあるか | N | |
-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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