登録情報 データベース : EMDB / ID : EMD-41142 ダウンロードとリンクタイトル APC/C-CDH1-UBE2C-UBE2S-Ubiquitin-CyclinB マップデータ 詳細 試料複合体 : Anaphase-Promoting Complex/Cyclosome in complex with CDH1, UBE2C, UBE2S, Cyclin-Bリガンド : x 1種 詳細 キーワード E3 RING Ligase / Ubiquitin Ligase / APC/C / Anaphase-Promoting Complex-Cyclosome / Cell Cycle / Cullin-RING ligase / LIGASE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 / Mitotic Prophase / regulation of chromosome condensation / positive regulation of anaphase-promoting complex-dependent catabolic process / G2/M DNA replication checkpoint / E2F-enabled inhibition of pre-replication complex formation / ventricular cardiac muscle cell development / Depolymerization of the Nuclear Lamina ... response to DDT / cyclin B1-CDK1 complex / positive regulation of mitochondrial ATP synthesis coupled electron transport / Mitotic Prophase / regulation of chromosome condensation / positive regulation of anaphase-promoting complex-dependent catabolic process / G2/M DNA replication checkpoint / E2F-enabled inhibition of pre-replication complex formation / ventricular cardiac muscle cell development / Depolymerization of the Nuclear Lamina / positive regulation of attachment of spindle microtubules to kinetochore / positive regulation of exit from mitosis / positive regulation of mRNA 3'-end processing / protein K27-linked ubiquitination / MASTL Facilitates Mitotic Progression / regulation of meiotic nuclear division / protein K29-linked ubiquitination / free ubiquitin chain polymerization / positive regulation of synapse maturation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint / 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 / positive regulation of synaptic plasticity / Phosphorylation of Emi1 / patched binding / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / protein branched polyubiquitination / metaphase/anaphase transition of mitotic cell cycle / regulation of meiotic cell cycle / anaphase-promoting complex-dependent catabolic process / lens fiber cell differentiation / Transcriptional regulation by RUNX2 / Phosphorylation of the APC/C / regulation of exit from mitosis / Nuclear Pore Complex (NPC) Disassembly / anaphase-promoting complex binding / tissue regeneration / outer kinetochore / protein K6-linked ubiquitination / (E3-independent) E2 ubiquitin-conjugating enzyme / positive regulation of mitotic metaphase/anaphase transition / positive regulation of dendrite morphogenesis / positive regulation of ubiquitin protein ligase activity / ubiquitin ligase activator activity / exit from mitosis / Initiation of Nuclear Envelope (NE) Reformation / Polo-like kinase mediated events / cyclin-dependent protein serine/threonine kinase activator activity / protein K11-linked ubiquitination / Golgi Cisternae Pericentriolar Stack Reorganization / cellular response to fatty acid / digestive tract development / Condensation of Prometaphase Chromosomes / oocyte maturation / 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 / microtubule organizing center / ubiquitin conjugating enzyme activity / Regulation of APC/C activators between G1/S and early anaphase / ubiquitin-like protein ligase binding / cullin family protein binding / Transcriptional Regulation by VENTX / negative regulation of cellular senescence / protein K63-linked ubiquitination / response to mechanical stimulus / ubiquitin ligase complex / enzyme-substrate adaptor activity / ubiquitin-like ligase-substrate adaptor activity / positive regulation of axon extension / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / protein K48-linked ubiquitination / heterochromatin / Cyclin A/B1/B2 associated events during G2/M transition / intercellular bridge / Cyclin A:Cdk2-associated events at S phase entry / Nuclear events stimulated by ALK signaling in cancer / positive regulation of cardiac muscle cell proliferation / positive regulation of G2/M transition of mitotic cell cycle / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / positive regulation of mitotic cell cycle / nuclear periphery / Resolution of Sister Chromatid Cohesion / regulation of mitotic cell cycle / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Condensation of Prophase Chromosomes / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / mitotic spindle organization / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / SCF-beta-TrCP mediated degradation of Emi1 / Assembly of the pre-replicative complex 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 domain / Anaphase-promoting complex subunit 5 / 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 11 RING-H2 finger / Anaphase-promoting complex subunit 2, C-terminal / Anaphase-promoting complex subunit 2 / Anaphase promoting complex (APC) subunit 2 / 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 / : / Cyclin, C-terminal domain / Tetratricopeptide repeat / : / Cyclins signature. / Cyclin / : / : / Cyclin, C-terminal domain / Cyclin_C / Cullin / Cullin, N-terminal / Cullin homology domain / Cullin homology domain superfamily / Cullin family / Cullin family profile. / Tetratricopeptide repeat / Tetratricopeptide repeat / Cyclin, N-terminal / Cyclin, N-terminal domain / Ubiquitin-conjugating enzyme, active site / Ubiquitin-conjugating (UBC) active site signature. / Ubiquitin-conjugating enzyme E2 / Ubiquitin-conjugating enzyme / Ubiquitin-conjugating (UBC) core domain profile. / Tetratricopeptide repeat / 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 / WD40-repeat-containing domain superfamily / Winged helix-like DNA-binding domain superfamily / WD40/YVTN repeat-like-containing 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 / Ubiquitin-conjugating enzyme E2 S / Anaphase-promoting complex subunit CDC26 / Anaphase-promoting complex subunit 16 / Anaphase-promoting complex subunit 13 / Anaphase-promoting complex subunit 1 ... 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 / Ubiquitin-conjugating enzyme E2 S / 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 : 3.5 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12月13日 - 現状 2023年12月13日 処理サイト : RCSB / 状態 : 公開
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