登録情報 データベース : EMDB / ID : EMD-41140 ダウンロードとリンクタイトル APC/C-CDH1-UBE2C-Ubiquitin-CyclinB-NTD マップデータ 詳細 試料複合体 : Anaphase-promoting complex/cyclosome in complex with CHD1, UBE2C, and Cyclin-Bリガンド : x 1種 詳細 キーワード E3 RING Ligase / Ubiquitin Ligase / LIGASE / TRANSFERASE機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
response to DDT / cyclin B1-CDK1 complex / positive regulation of mitochondrial ATP synthesis coupled electron transport / regulation of chromosome condensation / Mitotic Prophase / positive regulation of ubiquitin protein ligase activity / E2F-enabled inhibition of pre-replication complex formation / ventricular cardiac muscle cell development / Depolymerization of the Nuclear Lamina / positive regulation of anaphase-promoting complex-dependent catabolic process ... response to DDT / cyclin B1-CDK1 complex / positive regulation of mitochondrial ATP synthesis coupled electron transport / regulation of chromosome condensation / Mitotic Prophase / positive regulation of ubiquitin protein ligase activity / E2F-enabled inhibition of pre-replication complex formation / ventricular cardiac muscle cell development / Depolymerization of the Nuclear Lamina / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of synapse maturation / free ubiquitin chain polymerization / positive regulation of exit from mitosis / regulation of meiotic nuclear division / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint / positive regulation of mRNA 3'-end processing / positive regulation of attachment of spindle microtubules to kinetochore / MASTL Facilitates Mitotic Progression / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / Activation of NIMA Kinases NEK9, NEK6, NEK7 / anaphase-promoting complex / patched binding / Phosphorylation of Emi1 / Aberrant regulation of mitotic exit in cancer due to RB1 defects / anaphase-promoting complex-dependent catabolic process / regulation of meiotic cell cycle / protein branched polyubiquitination / lens fiber cell differentiation / metaphase/anaphase transition of mitotic cell cycle / Transcriptional regulation by RUNX2 / Nuclear Pore Complex (NPC) Disassembly / Phosphorylation of the APC/C / anaphase-promoting complex binding / tissue regeneration / G2/M DNA replication checkpoint / regulation of exit from mitosis / outer kinetochore / (E3-independent) E2 ubiquitin-conjugating enzyme / positive regulation of synaptic plasticity / positive regulation of dendrite morphogenesis / Polo-like kinase mediated events / exit from mitosis / Initiation of Nuclear Envelope (NE) Reformation / cellular response to fatty acid / cyclin-dependent protein serine/threonine kinase activator activity / Golgi Cisternae Pericentriolar Stack Reorganization / positive regulation of mitotic metaphase/anaphase transition / protein K11-linked ubiquitination / oocyte maturation / digestive tract development / ubiquitin ligase activator activity / Condensation of Prometaphase Chromosomes / regulation of mitotic metaphase/anaphase transition / cyclin-dependent protein serine/threonine kinase regulator activity / ubiquitin-ubiquitin ligase activity / E2 ubiquitin-conjugating enzyme / mitotic metaphase chromosome alignment / mitotic G2 DNA damage checkpoint signaling / Regulation of APC/C activators between G1/S and early anaphase / ubiquitin conjugating enzyme activity / Transcriptional Regulation by VENTX / negative regulation of cellular senescence / microtubule organizing center / ubiquitin-like protein ligase binding / cullin family protein binding / positive regulation of G2/M transition of mitotic cell cycle / enzyme-substrate adaptor activity / ubiquitin ligase complex / response to mechanical stimulus / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / positive regulation of axon extension / Cyclin A:Cdk2-associated events at S phase entry / positive regulation of cardiac muscle cell proliferation / intercellular bridge / Cyclin A/B1/B2 associated events during G2/M transition / ubiquitin-like ligase-substrate adaptor activity / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / heterochromatin / Nuclear events stimulated by ALK signaling in cancer / protein K48-linked ubiquitination / positive regulation of mitotic cell cycle / nuclear periphery / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / regulation of mitotic cell cycle / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / Resolution of Sister Chromatid Cohesion / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Condensation of Prophase Chromosomes / mitotic spindle organization / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / cellular response to iron(III) ion / SCF-beta-TrCP mediated degradation of Emi1 / Assembly of the pre-replicative complex / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / G1/S transition of mitotic cell cycle / brain development 類似検索 - 分子機能 : / Anaphase-promoting complex subunit 15 / Anaphase-promoting complex subunit 15 / : / CDC20/Fizzy WD40 domain / The WD repeat Cdc20/Fizzy family / : / APC4, WD40 domain C-terminal half / Anaphase-promoting complex subunit 4, metazoa / Anaphase-promoting complex subunit 1, C-terminal ... : / Anaphase-promoting complex subunit 15 / Anaphase-promoting complex subunit 15 / : / CDC20/Fizzy WD40 domain / The WD repeat Cdc20/Fizzy family / : / APC4, WD40 domain C-terminal half / Anaphase-promoting complex subunit 4, metazoa / Anaphase-promoting complex subunit 1, C-terminal / Anaphase-promoting complex subunit 1, middle domain / : / : / : / Anaphase-promoting complex subunit 1 WD40 beta-propeller domain / Anaphase-promoting complex sub unit 1 C-terminal domain / Anaphase-promoting complex subunit 1 middle domain / APC1 beta sandwich domain / Anaphase-promoting complex subunit 5, N-terminal domain / Anaphase-promoting complex subunit 16 / Anaphase-promoting complex, subunit 16 / Cdc23 / Apc13 / Anaphase promoting complex subunit 8 / Cdc23 / Apc13p protein / Anaphase-promoting complex subunit 4 / Anaphase-promoting complex subunit 4 long domain / Anaphase-promoting complex subunit 1 / Anaphase-promoting complex subunit 5 / Anaphase-promoting complex, cyclosome, subunit 4 / Anaphase-promoting complex subunit APC10/Doc1 / Anaphase-promoting complex, subunit CDC26 / Anaphase-promoting complex APC subunit CDC26 / Anaphase-promoting complex subunit 11, RING-H2 finger / Anaphase-promoting complex subunit 5 domain / Anaphase-promoting complex subunit 11 RING-H2 finger / Anaphase-promoting complex subunit 5 / Anaphase-promoting complex subunit 2, C-terminal / Anaphase-promoting complex subunit 2 / : / Anaphase promoting complex (APC) subunit 2 / ANAPC2-like, TPR repeats / Anaphase promoting complex (APC) subunit 2 / APC10/DOC domain / Anaphase-promoting complex, subunit 10 (APC10) / DOC domain profile. / Anaphase-promoting complex, subunit 10 (APC10) / Anaphase-promoting complex, cyclosome, subunit 3 / TPR repeat / Anaphase-promoting complex subunit 4, WD40 domain / Anaphase-promoting complex subunit 4 WD40 domain / : / Tetratricopeptide repeat / : / Cyclin, C-terminal domain / : / Cyclins signature. / Cyclin / Cyclin, C-terminal domain / Cyclin_C / : / Tetratricopeptide repeat / Cullin / : / Cullin alpha+beta domain / Cullin homology domain / Cullin homology domain superfamily / Cullin family profile. / Tetratricopeptide repeat / Cyclin, N-terminal / Cyclin, N-terminal domain / Ubiquitin-conjugating enzyme, active site / Ubiquitin-conjugating (UBC) active site signature. / Tetratricopeptide repeat / Ubiquitin-conjugating enzyme E2 / Ubiquitin-conjugating enzyme / Ubiquitin-conjugating (UBC) core domain profile. / Ubiquitin-conjugating enzyme E2, catalytic domain homologues / Cyclin-like / domain present in cyclins, TFIIB and Retinoblastoma / Ubiquitin-conjugating enzyme/RWD-like / Cyclin-like superfamily / TPR repeat region circular profile. / TPR repeat profile. / Tetratricopeptide repeats / Tetratricopeptide repeat / Galactose-binding-like domain superfamily / Zinc finger RING-type profile. / Zinc finger, RING-type / Armadillo-like helical / Tetratricopeptide-like helical domain superfamily / Zinc finger, RING/FYVE/PHD-type / Winged helix DNA-binding domain superfamily / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / Winged helix-like DNA-binding domain superfamily 類似検索 - ドメイン・相同性 Ubiquitin-conjugating enzyme E2 C / G2/mitotic-specific cyclin-B1 / Cell division cycle protein 27 homolog / Anaphase-promoting complex subunit 15 / Cell division cycle protein 16 homolog / Anaphase-promoting complex subunit CDC26 / Anaphase-promoting complex subunit 16 / Anaphase-promoting complex subunit 13 / Anaphase-promoting complex subunit 1 / Anaphase-promoting complex subunit 11 ... Ubiquitin-conjugating enzyme E2 C / G2/mitotic-specific cyclin-B1 / Cell division cycle protein 27 homolog / Anaphase-promoting complex subunit 15 / Cell division cycle protein 16 homolog / Anaphase-promoting complex subunit CDC26 / Anaphase-promoting complex subunit 16 / Anaphase-promoting complex subunit 13 / Anaphase-promoting complex subunit 1 / Anaphase-promoting complex subunit 11 / Cell division cycle protein 23 homolog / Anaphase-promoting complex subunit 7 / Anaphase-promoting complex subunit 5 / Anaphase-promoting complex subunit 4 / Anaphase-promoting complex subunit 2 / Fizzy-related protein homolog / Anaphase-promoting complex subunit 10 類似検索 - 構成要素生物種 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 : 4.0 Å 詳細 データ登録者Bodrug T / Welsh KA / Bolhuis DL / Paulakonis E / Martinez-Chacin RC / Liu B / Pinkin N / Bonacci T / Cui L / Xu P ...Bodrug T / Welsh KA / Bolhuis DL / Paulakonis E / Martinez-Chacin RC / Liu B / Pinkin N / Bonacci T / Cui L / Xu P / Roscow O / Amann SJ / Grishkovskaya I / Emanuele MJ / Harrison JS / Steimel JP / Hahn KM / Zhang W / Zhong E / Haselbach D / Brown NG 資金援助 米国, オーストリア, 4件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD) T32GM008570 米国 Vienna Science and Technology Fund (WWTF) WWTF-LS19-029 オーストリア National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD) R35GM128855 米国 National Science Foundation (NSF, United States) DGE-1650116 米国
引用ジャーナル : Nat Struct Mol Biol / 年 : 2023タイトル : Time-resolved cryo-EM (TR-EM) analysis of substrate polyubiquitination by the RING E3 anaphase-promoting complex/cyclosome (APC/C).著者: Tatyana Bodrug / Kaeli A Welsh / Derek L Bolhuis / Ethan Paulаkonis / Raquel C Martinez-Chacin / Bei Liu / Nicholas Pinkin / Thomas Bonacci / Liying Cui / Pengning Xu / Olivia Roscow / ... 著者 : Tatyana Bodrug / Kaeli A Welsh / Derek L Bolhuis / Ethan Paulаkonis / Raquel C Martinez-Chacin / Bei Liu / Nicholas Pinkin / Thomas Bonacci / Liying Cui / Pengning Xu / Olivia Roscow / Sascha Josef Amann / Irina Grishkovskaya / Michael J Emanuele / Joseph S Harrison / Joshua P Steimel / Klaus M Hahn / Wei Zhang / Ellen D Zhong / David Haselbach / Nicholas G Brown / 要旨 : Substrate polyubiquitination drives a myriad of cellular processes, including the cell cycle, apoptosis and immune responses. Polyubiquitination is highly dynamic, and obtaining mechanistic insight ... Substrate polyubiquitination drives a myriad of cellular processes, including the cell cycle, apoptosis and immune responses. Polyubiquitination is highly dynamic, and obtaining mechanistic insight has thus far required artificially trapped structures to stabilize specific steps along the enzymatic process. So far, how any ubiquitin ligase builds a proteasomal degradation signal, which is canonically regarded as four or more ubiquitins, remains unclear. Here we present time-resolved cryogenic electron microscopy studies of the 1.2 MDa E3 ubiquitin ligase, known as the anaphase-promoting complex/cyclosome (APC/C), and its E2 co-enzymes (UBE2C/UBCH10 and UBE2S) during substrate polyubiquitination. Using cryoDRGN (Deep Reconstructing Generative Networks), a neural network-based approach, we reconstruct the conformational changes undergone by the human APC/C during polyubiquitination, directly visualize an active E3-E2 pair modifying its substrate, and identify unexpected interactions between multiple ubiquitins with parts of the APC/C machinery, including its coactivator CDH1. Together, we demonstrate how modification of substrates with nascent ubiquitin chains helps to potentiate processive substrate polyubiquitination, allowing us to model how a ubiquitin ligase builds a proteasomal degradation signal. 履歴 登録 2023年6月27日 - ヘッダ(付随情報) 公開 2023年9月27日 - マップ公開 2023年9月27日 - 更新 2023年11月22日 - 現状 2023年11月22日 処理サイト : RCSB / 状態 : 公開
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