+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-3433 | |||||||||
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タイトル | Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2S-Ubiquitin (variant)-substrate | |||||||||
マップデータ | Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2S-Ubiquitin (variant)-substrate | |||||||||
試料 |
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キーワード | Anaphase Promoting Complex / ubiquitin ligation | |||||||||
機能・相同性 | 機能・相同性情報 protein localization to septin ring / mitotic morphogenesis checkpoint signaling / cellular bud neck septin ring / positive regulation of anaphase-promoting complex-dependent catabolic process / protein K27-linked ubiquitination / regulation of meiotic nuclear division / free ubiquitin chain polymerization / protein K29-linked ubiquitination / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint ...protein localization to septin ring / mitotic morphogenesis checkpoint signaling / cellular bud neck septin ring / positive regulation of anaphase-promoting complex-dependent catabolic process / protein K27-linked ubiquitination / regulation of meiotic nuclear division / free ubiquitin chain polymerization / protein K29-linked ubiquitination / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint / positive regulation of synapse maturation / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / Phosphorylation of Emi1 / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / regulation of meiotic cell cycle / metaphase/anaphase transition of mitotic cell cycle / anaphase-promoting complex-dependent catabolic process / lens fiber cell differentiation / positive regulation of synaptic plasticity / regulation of exit from mitosis / anaphase-promoting complex binding / Phosphorylation of the APC/C / protein K6-linked ubiquitination / cellular bud neck / ubiquitin ligase activator activity / positive regulation of mitotic metaphase/anaphase transition / positive regulation of ubiquitin protein ligase activity / protein K11-linked ubiquitination / enzyme-substrate adaptor activity / hypothalamus gonadotrophin-releasing hormone neuron development / regulation of mitotic metaphase/anaphase transition / positive regulation of dendrite morphogenesis / female meiosis I / positive regulation of protein monoubiquitination / mitochondrion transport along microtubule / exit from mitosis / ubiquitin-ubiquitin ligase activity / fat pad development / mitotic metaphase chromosome alignment / E2 ubiquitin-conjugating enzyme / female gonad development / seminiferous tubule development / male meiosis I / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / mitotic G2 DNA damage checkpoint signaling / negative regulation of cellular senescence / cullin family protein binding / Regulation of APC/C activators between G1/S and early anaphase / ubiquitin conjugating enzyme activity / protein K63-linked ubiquitination / ubiquitin-like ligase-substrate adaptor activity / Transcriptional Regulation by VENTX / positive regulation of axon extension / protein K48-linked ubiquitination / heterochromatin / regulation of neuron apoptotic process / energy homeostasis / Regulation of pyruvate metabolism / regulation of proteasomal protein catabolic process / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Cyclin A:Cdk2-associated events at S phase entry / 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 / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / 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 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / regulation of mitotic cell cycle / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / PINK1-PRKN Mediated Mitophagy / 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 / NF-kB is activated and signals survival / NRIF signals cell death from the nucleus 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: 6.0 Å | |||||||||
データ登録者 | Brown N / VanderLinden R / Watson E / Weissmann F / Ordureau A / Wu K-P / Yu S / Mercedi P / Harrison J / Davidson I ...Brown N / VanderLinden R / Watson E / Weissmann F / Ordureau A / Wu K-P / Yu S / Mercedi P / Harrison J / Davidson I / Coudevylle R / Lu Y / Dube P / Brunner M / Grace CRR / Miller D / Haselbach D / Jarvis M / Yamaguchi M / Yanishevski D / Petzold G / Sidhu S / Kuhlman B / Kirschner M / Harper JW / Peters J-M / Stark H / Schulman BA | |||||||||
引用 | ジャーナル: Cell / 年: 2016 タイトル: Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C. 著者: Nicholas G Brown / Ryan VanderLinden / Edmond R Watson / Florian Weissmann / Alban Ordureau / Kuen-Phon Wu / Wei Zhang / Shanshan Yu / Peter Y Mercredi / Joseph S Harrison / Iain F Davidson / ...著者: Nicholas G Brown / Ryan VanderLinden / Edmond R Watson / Florian Weissmann / Alban Ordureau / Kuen-Phon Wu / Wei Zhang / Shanshan Yu / Peter Y Mercredi / Joseph S Harrison / Iain F Davidson / Renping Qiao / Ying Lu / Prakash Dube / Michael R Brunner / Christy R R Grace / Darcie J Miller / David Haselbach / Marc A Jarvis / Masaya Yamaguchi / David Yanishevski / Georg Petzold / Sachdev S Sidhu / Brian Kuhlman / Marc W Kirschner / J Wade Harper / Jan-Michael Peters / Holger Stark / Brenda A Schulman / 要旨: Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of ...Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C) and its two partner E2s, UBE2C (aka UBCH10) and UBE2S, adopt specialized catalytic architectures for these two distinct forms of polyubiquitination. The APC/C RING constrains UBE2C proximal to a substrate and simultaneously binds a substrate-linked UB to drive processive multiubiquitination. Alternatively, during UB chain elongation, the RING does not bind UBE2S but rather lures an evolving substrate-linked UB to UBE2S positioned through a cullin interaction to generate a Lys11-linked chain. Our findings define mechanisms of APC/C regulation, and establish principles by which specialized E3-E2-substrate-UB architectures control different forms of polyubiquitination. | |||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_3433.map.gz | 57.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-3433-v30.xml emd-3433.xml | 9.9 KB 9.9 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_3433.png | 436 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-3433 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-3433 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_3433_validation.pdf.gz | 249 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_3433_full_validation.pdf.gz | 248.1 KB | 表示 | |
XML形式データ | emd_3433_validation.xml.gz | 5.9 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3433 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3433 | HTTPS FTP |
-関連構造データ
-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_3433.map.gz / 形式: CCP4 / 大きさ: 62.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2S-Ubiquitin (variant)-substrate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.57 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
-全体 : Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2S-Ubiquitin...
全体 | 名称: Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2S-Ubiquitin (variant)-substrate |
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要素 |
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-超分子 #1000: Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2S-Ubiquitin...
超分子 | 名称: Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2S-Ubiquitin (variant)-substrate タイプ: sample / ID: 1000 / Number unique components: 1 |
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分子量 | 実験値: 1.5 MDa |
-分子 #1: Anaphase Promoting Complex
分子 | 名称: Anaphase Promoting Complex / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 組換発現: Yes |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 別称: Human |
-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
濃度 | 0.1 mg/mL |
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緩衝液 | pH: 8 / 詳細: 50 mM Hepes, 150 mM NaCl, 2 mM MgCl2 |
グリッド | 詳細: 200 mesh copper grids, quantifoil with thin carbon support |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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日付 | 2015年7月31日 |
撮影 | カテゴリ: CCD フィルム・検出器のモデル: FEI FALCON II (4k x 4k) 実像数: 2070 / 平均電子線量: 40 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 倍率(補正後): 89000 / 照射モード: SPOT SCAN / 撮影モード: BRIGHT FIELD / Cs: 0.0001 mm / 最大 デフォーカス(公称値): 3.5 µm / 最小 デフォーカス(公称値): 0.7 µm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
CTF補正 | 詳細: each particle |
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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: 6.0 Å / 解像度の算出法: OTHER / 使用した粒子像数: 125390 |