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Open data
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Basic information
| Entry | Database: PDB / ID: 8tar | |||||||||||||||
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| Title | APC/C-CDH1-UBE2C-Ubiquitin-CyclinB-NTD | |||||||||||||||
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Keywords | TRANSFERASE / E3 RING Ligase / Ubiquitin Ligase / LIGASE | |||||||||||||||
| Function / homology | Function and homology informationresponse to DDT / regulation of chromosome condensation / cyclin B1-CDK1 complex / positive regulation of mitochondrial ATP synthesis coupled electron transport / Mitotic Prophase / ventricular cardiac muscle cell development / positive regulation of ubiquitin protein ligase activity / E2F-enabled inhibition of pre-replication complex formation / positive regulation of anaphase-promoting complex-dependent catabolic process / Depolymerization of the Nuclear Lamina ...response to DDT / regulation of chromosome condensation / cyclin B1-CDK1 complex / positive regulation of mitochondrial ATP synthesis coupled electron transport / Mitotic Prophase / ventricular cardiac muscle cell development / positive regulation of ubiquitin protein ligase activity / E2F-enabled inhibition of pre-replication complex formation / positive regulation of anaphase-promoting complex-dependent catabolic process / Depolymerization of the Nuclear Lamina / positive regulation of synapse maturation / free ubiquitin chain polymerization / positive regulation of exit from mitosis / positive regulation of mRNA 3'-end processing / regulation of mitotic cell cycle spindle assembly checkpoint / positive regulation of attachment of spindle microtubules to kinetochore / MASTL Facilitates Mitotic Progression / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / 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 / tissue regeneration / exit from mitosis / anaphase-promoting complex / patched binding / Phosphorylation of Emi1 / anaphase-promoting complex-dependent catabolic process / metaphase/anaphase transition of mitotic cell cycle / oocyte maturation / regulation of meiotic cell cycle / protein branched polyubiquitination / Aberrant regulation of mitotic exit in cancer due to RB1 defects / Transcriptional regulation by RUNX2 / regulation of exit from mitosis / anaphase-promoting complex binding / Nuclear Pore Complex (NPC) Disassembly / G2/M DNA replication checkpoint / Phosphorylation of the APC/C / outer kinetochore / positive regulation of synaptic plasticity / (E3-independent) E2 ubiquitin-conjugating enzyme / positive regulation of dendrite morphogenesis / digestive tract development / Initiation of Nuclear Envelope (NE) Reformation / Polo-like kinase mediated events / positive regulation of mitotic metaphase/anaphase transition / Golgi Cisternae Pericentriolar Stack Reorganization / cellular response to fatty acid / cyclin-dependent protein serine/threonine kinase activator activity / protein K11-linked ubiquitination / cellular response to iron(III) ion / negative regulation of cellular senescence / ubiquitin ligase activator activity / Condensation of Prometaphase Chromosomes / cyclin-dependent protein serine/threonine kinase regulator activity / regulation of mitotic metaphase/anaphase transition / E2 ubiquitin-conjugating enzyme / ubiquitin-ubiquitin ligase activity / intercellular bridge / mitotic G2 DNA damage checkpoint signaling / positive regulation of cardiac muscle cell proliferation / Regulation of APC/C activators between G1/S and early anaphase / microtubule organizing center / ubiquitin conjugating enzyme activity / Transcriptional Regulation by VENTX / ubiquitin-like protein ligase binding / response to mechanical stimulus / cullin family protein binding / mitotic metaphase chromosome alignment / enzyme-substrate adaptor activity / positive regulation of axon extension / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / ubiquitin ligase complex / Cyclin A:Cdk2-associated events at S phase entry / positive regulation of G2/M transition of mitotic cell cycle / 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 / positive regulation of mitotic cell cycle / heterochromatin / Nuclear events stimulated by ALK signaling in cancer / protein K48-linked ubiquitination / nuclear periphery / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / Resolution of Sister Chromatid Cohesion / mitotic spindle organization / regulation of mitotic cell cycle / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Condensation of Prophase Chromosomes / brain development / G1/S transition of mitotic cell cycle / G2/M transition of mitotic cell cycle / 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 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 Similarity search - Function | |||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | |||||||||||||||
Authors | Bodrug, T. / Welsh, K.A. / Bolhuis, D.L. / Paulakonis, E. / Martinez-Chacin, R.C. / Liu, B. / Pinkin, N. / Bonacci, T. / Cui, L. / Xu, P. ...Bodrug, T. / Welsh, K.A. / Bolhuis, D.L. / Paulakonis, E. / Martinez-Chacin, R.C. / Liu, B. / Pinkin, N. / Bonacci, T. / Cui, L. / Xu, P. / Roscow, O. / Amann, S.J. / Grishkovskaya, I. / Emanuele, M.J. / Harrison, J.S. / Steimel, J.P. / Hahn, K.M. / Zhang, W. / Zhong, E. / Haselbach, D. / Brown, N.G. | |||||||||||||||
| Funding support | United States, Austria, 4items
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Citation | Journal: Nat Struct Mol Biol / Year: 2023Title: Time-resolved cryo-EM (TR-EM) analysis of substrate polyubiquitination by the RING E3 anaphase-promoting complex/cyclosome (APC/C). Authors: 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 / ...Authors: 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 / ![]() Abstract: 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. | |||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 8tar.cif.gz | 1.5 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb8tar.ent.gz | 1 MB | Display | PDB format |
| PDBx/mmJSON format | 8tar.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ta/8tar ftp://data.pdbj.org/pub/pdb/validation_reports/ta/8tar | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 41140MC ![]() 8tauC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Anaphase-promoting complex subunit ... , 11 types, 13 molecules ACDGWHILMNOYZ
| #1: Protein | Mass: 217566.141 Da / Num. of mol.: 1 Mutation: S202E, S286E, T291E, S313E, T316E, S317E, S334E, S341E, S343E, S355E, S362E, S372E, S377E, T537E, S547E, S555E, S569E, S688E, S699E, S916E, S1347E Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC1 / Production host: ![]() | ||||||||||||||
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| #3: Protein | Mass: 9854.647 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC11, HSPC214 / Production host: ![]() | ||||||||||||||
| #4: Protein | Mass: 6556.302 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC15 / Production host: ![]() | ||||||||||||||
| #5: Protein | Mass: 9920.108 Da / Num. of mol.: 2 / Mutation: S51E, S52E, S82E Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDC26, ANAPC12, C9orf17 / Production host: ![]() #6: Protein | | Mass: 6764.688 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC16, C10orf104, CENP-27 / Production host: ![]() #7: Protein | | Mass: 92303.305 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC4, APC4 / Production host: ![]() #10: Protein | | Mass: 21310.152 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC10, APC10 / Production host: ![]() #11: Protein | | Mass: 8528.309 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC13 / Production host: ![]() #12: Protein | | Mass: 94149.156 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC2, APC2, KIAA1406 / Production host: ![]() #13: Protein | | Mass: 85445.961 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC5, APC5 / Production host: ![]() #17: Protein | Mass: 63204.020 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC7, APC7 / Production host: ![]() |
-Cell division cycle protein ... , 3 types, 6 molecules JPKSUV
| #8: Protein | Mass: 92519.547 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDC27, ANAPC3, D0S1430E, D17S978E / Production host: ![]() #9: Protein | Mass: 71929.656 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDC16, ANAPC6 / Production host: ![]() #16: Protein | Mass: 69075.133 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDC23, ANAPC8 / Production host: ![]() |
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-Protein , 2 types, 2 molecules QR
| #14: Protein | Mass: 16346.630 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: UBE2C / Production host: ![]() |
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| #15: Protein | Mass: 55253.207 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FZR1 / Production host: ![]() |
-Protein/peptide / Non-polymers , 2 types, 5 molecules B

| #18: Chemical | ChemComp-ZN / #2: Protein/peptide | | Mass: 1284.467 Da / Num. of mol.: 1 / Fragment: NTD (residues 39-50) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CCNB1, CCNB / Production host: ![]() |
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-Details
| Has ligand of interest | N |
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-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: Anaphase-promoting complex/cyclosome in complex with CHD1, UBE2C, and Cyclin-B Type: COMPLEX / Entity ID: #1-#17 / Source: RECOMBINANT |
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| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: ![]() |
| Buffer solution | pH: 8 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: FEI TITAN KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 200 nm |
| Image recording | Electron dose: 42 e/Å2 / Film or detector model: GATAN K2 BASE (4k x 4k) |
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Processing
| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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| 3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 661289 / Symmetry type: POINT |
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About Yorodumi




Homo sapiens (human)
United States,
Austria, 4items
Citation



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FIELD EMISSION GUN