+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-3432 | |||||||||
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タイトル | Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2C (aka UBCH10)-substrate-Ubiquitin (variant) | |||||||||
マップデータ | Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2C (aka UBCH10)-substrate-Ubiquitin (variant) | |||||||||
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 Translesion synthesis by REV1 / Recognition of DNA damage by PCNA-containing replication complex / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / Activated NOTCH1 Transmits Signal to the Nucleus / Downregulation of TGF-beta receptor signaling / Regulation of FZD by ubiquitination / Regulation of TNFR1 signaling / TNFR1-induced NF-kappa-B signaling pathway / Translesion synthesis by POLK ...Translesion synthesis by REV1 / Recognition of DNA damage by PCNA-containing replication complex / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / Activated NOTCH1 Transmits Signal to the Nucleus / Downregulation of TGF-beta receptor signaling / Regulation of FZD by ubiquitination / Regulation of TNFR1 signaling / TNFR1-induced NF-kappa-B signaling pathway / Translesion synthesis by POLK / Translesion synthesis by POLI / Termination of translesion DNA synthesis / Gap-filling DNA repair synthesis and ligation in GG-NER / Formation of TC-NER Pre-Incision Complex / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / Fanconi Anemia Pathway / Regulation of TP53 Degradation / Regulation of TP53 Activity through Methylation / Cyclin D associated events in G1 / Stabilization of p53 / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / ER Quality Control Compartment (ERQC) / Interferon alpha/beta signaling / Endosomal Sorting Complex Required For Transport (ESCRT) / Negative regulators of DDX58/IFIH1 signaling / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / IKK complex recruitment mediated by RIP1 / IRAK2 mediated activation of TAK1 complex / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Alpha-protein kinase 1 signaling pathway / Inactivation of CSF3 (G-CSF) signaling / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Regulation of NF-kappa B signaling / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / NOD1/2 Signaling Pathway / activated TAK1 mediates p38 MAPK activation / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / DNA Damage Recognition in GG-NER / Formation of Incision Complex in GG-NER / Dual Incision in GG-NER / E3 ubiquitin ligases ubiquitinate target proteins / Translesion Synthesis by POLH / Downregulation of ERBB2:ERBB3 signaling / TCF dependent signaling in response to WNT / Regulation of innate immune responses to cytosolic DNA / HDR through Homologous Recombination (HRR) / Downregulation of ERBB2 signaling / Regulation of signaling by CBL / Ovarian tumor domain proteases / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / NOTCH3 Activation and Transmission of Signal to the Nucleus / Interleukin-1 signaling / protein localization to septin ring / Downregulation of ERBB4 signaling / Deactivation of the beta-catenin transactivating complex / Negative regulation of MET activity / Regulation of PTEN localization / Josephin domain DUBs / mitotic morphogenesis checkpoint signaling / Pexophagy / Stimuli-sensing channels / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Metalloprotease DUBs / Regulation of necroptotic cell death / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Autodegradation of Cdh1 by Cdh1:APC/C / SCF-beta-TrCP mediated degradation of Emi1 / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / SCF(Skp2)-mediated degradation of p27/p21 / NRIF signals cell death from the nucleus / NF-kB is activated and signals survival / Autodegradation of the E3 ubiquitin ligase COP1 / Asymmetric localization of PCP proteins / Degradation of DVL / Hedgehog ligand biogenesis / Dectin-1 mediated noncanonical NF-kB signaling / Degradation of GLI1 by the proteasome / Hedgehog 'on' state / TNFR2 non-canonical NF-kB pathway / NIK-->noncanonical NF-kB signaling / UCH proteinases / Assembly of the pre-replicative complex / CDK-mediated phosphorylation and removal of Cdc6 / G2/M Checkpoints / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Ubiquitin-dependent degradation of Cyclin D / The role of GTSE1 in G2/M progression after G2 checkpoint / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Regulation of RUNX3 expression and activity / Aggrephagy / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / p75NTR recruits signalling complexes / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / GLI3 is processed to GLI3R by the proteasome / Activation of NF-kappaB in B cells 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: 6.4 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_3432.map.gz | 58.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-3432-v30.xml emd-3432.xml | 9.9 KB 9.9 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_3432.png | 435.2 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-3432 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-3432 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_3432_validation.pdf.gz | 244.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_3432_full_validation.pdf.gz | 243.8 KB | 表示 | |
XML形式データ | emd_3432_validation.xml.gz | 6.1 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3432 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3432 | 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_3432.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-UBE2C (aka UBCH10)-substrate-Ubiquitin (variant) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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-UBE2C (aka UBCH...
全体 | 名称: Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2C (aka UBCH10)-substrate-Ubiquitin (variant) |
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要素 |
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-超分子 #1000: Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2C (aka UBCH...
超分子 | 名称: Anaphase-promoting complex/Cyclosome (APC/C)-CDH1-UBE2C (aka UBCH10)-substrate-Ubiquitin (variant) 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 / 組換発現: Yes |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 別称: Human |
分子量 | 実験値: 1.5 MDa |
-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: 8 / 詳細: 50 mM HEPES, 200 mM NaCl, 2 mM MgCl2 |
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グリッド | 詳細: quantifoil 3.5/1, with continuous 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9月13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: 4066 / 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: 0.00001 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 micrograph |
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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: 6.4 Å / 解像度の算出法: OTHER / ソフトウェア - 名称: Relion / 使用した粒子像数: 135578 |