+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-17822 | |||||||||
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タイトル | K48-linked ubiquitin chain formation with a cullin-RING E3 ligase and Cdc34: NEDD8-CUL2-RBX1-ELOB/C-FEM1C with trapped UBE2R2-donor UB-acceptor UB-SIL1 peptide | |||||||||
マップデータ | Composite Map | |||||||||
試料 |
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キーワード | CUL2 / FEM1C / ELOBC / SIL1 / Ubiquitin (ユビキチン) / Ubiquitin Ligase (ユビキチンリガーゼ) / Ubiquitin chain formation / Poliubiquitylation / LIGASE (リガーゼ) | |||||||||
機能・相同性 | 機能・相同性情報 adenyl-nucleotide exchange factor activity / cotranslational protein targeting to membrane / 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 / target-directed miRNA degradation ...adenyl-nucleotide exchange factor activity / cotranslational protein targeting to membrane / 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 / target-directed miRNA degradation / elongin complex / VCB complex / positive regulation of protein autoubiquitination / protein neddylation / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin-ubiquitin ligase activity / 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 / Prolactin receptor signaling / ubiquitin conjugating enzyme activity / protein monoubiquitination / cullin family protein binding / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / ubiquitin-like ligase-substrate adaptor activity / protein K48-linked ubiquitination / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / Formation of HIV elongation complex in the absence of HIV Tat / Nuclear events stimulated by ALK signaling in cancer / ubiquitin ligase complex / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation 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 / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / positive regulation of TORC1 signaling / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / RNA Polymerase II Pre-transcription Events / 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 / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / 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 / Downregulation of TGF-beta receptor signaling / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / 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 / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 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: 3.76 Å | |||||||||
データ登録者 | Liwocha J / Prabu JR / Kleiger G / Schulman BA | |||||||||
資金援助 | ドイツ, 1件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2024 タイトル: Mechanism of millisecond Lys48-linked poly-ubiquitin chain formation by cullin-RING ligases. 著者: Joanna Liwocha / Jerry Li / Nicholas Purser / Chutima Rattanasopa / Samuel Maiwald / David T Krist / Daniel C Scott / Barbara Steigenberger / J Rajan Prabu / Brenda A Schulman / Gary Kleiger / 要旨: E3 ubiquitin ligases, in collaboration with E2 ubiquitin-conjugating enzymes, modify proteins with poly-ubiquitin chains. Cullin-RING ligase (CRL) E3s use Cdc34/UBE2R-family E2s to build Lys48-linked ...E3 ubiquitin ligases, in collaboration with E2 ubiquitin-conjugating enzymes, modify proteins with poly-ubiquitin chains. Cullin-RING ligase (CRL) E3s use Cdc34/UBE2R-family E2s to build Lys48-linked poly-ubiquitin chains to control an enormous swath of eukaryotic biology. Yet the molecular mechanisms underlying this exceptional linkage specificity and millisecond kinetics of poly-ubiquitylation remain unclear. Here we obtain cryogenic-electron microscopy (cryo-EM) structures that provide pertinent insight into how such poly-ubiquitin chains are forged. The CRL RING domain not only activates the E2-bound ubiquitin but also shapes the conformation of a distinctive UBE2R2 loop, positioning both the ubiquitin to be transferred and the substrate-linked acceptor ubiquitin within the active site. The structures also reveal how the ubiquitin-like protein NEDD8 uniquely activates CRLs during chain formation. NEDD8 releases the RING domain from the CRL, but unlike previous CRL-E2 structures, does not contact UBE2R2. These findings suggest how poly-ubiquitylation may be accomplished by many E2s and E3s. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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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_17822.map.gz | 185.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-17822-v30.xml emd-17822.xml | 35.2 KB 35.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_17822.png | 65.1 KB | ||
Filedesc metadata | emd-17822.cif.gz | 7.8 KB | ||
その他 | emd_17822_additional_1.map.gz emd_17822_additional_2.map.gz emd_17822_additional_3.map.gz emd_17822_additional_4.map.gz emd_17822_additional_5.map.gz | 182.7 MB 181.9 MB 182.7 MB 182.7 MB 182.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-17822 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-17822 | HTTPS FTP |
-関連構造データ
関連構造データ | 8pqlMC C: 同じ文献を引用 (文献) M: このマップから作成された原子モデル |
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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
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 |
-マップ
ファイル | ダウンロード / ファイル: emd_17822.map.gz / 形式: CCP4 / 大きさ: 209.3 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | Composite Map | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.851 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
-追加マップ: Focused map 5
ファイル | emd_17822_additional_1.map | ||||||||||||
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注釈 | Focused map 5 | ||||||||||||
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密度ヒストグラム |
-追加マップ: Focused map 1
ファイル | emd_17822_additional_2.map | ||||||||||||
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注釈 | Focused map 1 | ||||||||||||
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密度ヒストグラム |
-追加マップ: Focused map 2
ファイル | emd_17822_additional_3.map | ||||||||||||
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注釈 | Focused map 2 | ||||||||||||
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密度ヒストグラム |
-追加マップ: Focused map 3
ファイル | emd_17822_additional_4.map | ||||||||||||
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注釈 | Focused map 3 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Focused map 4
ファイル | emd_17822_additional_5.map | ||||||||||||
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注釈 | Focused map 4 | ||||||||||||
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密度ヒストグラム |
-試料の構成要素
+全体 : K48-linked ubiquitin chain formation with a cullin-RING E3 ligase...
+超分子 #1: K48-linked ubiquitin chain formation with a cullin-RING E3 ligase...
+超分子 #2: RING E3 ligase (RBX1) and Cullin-2 (CUL2)
+超分子 #3: CDC34, NEDD8, ELOB, ELOC, FEM1C with UBE2R2-donor UB-acceptor UB-...
+分子 #1: Ubiquitin-conjugating enzyme E2 R2
+分子 #2: Polyubiquitin-C,Nucleotide exchange factor SIL1
+分子 #3: Protein fem-1 homolog C
+分子 #4: E3 ubiquitin-protein ligase RBX1
+分子 #5: Ubiquitin
+分子 #6: Cullin-2
+分子 #7: Elongin-C
+分子 #8: Elongin-B
+分子 #9: 5-azanylpentan-2-one
+分子 #10: 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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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE-PROPANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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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: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy / 最大 デフォーカス(公称値): 2.6 µm / 最小 デフォーカス(公称値): 0.6 µm |
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 60.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.76 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 61956 |