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Open data
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Basic information
Entry | Database: PDB / ID: 9n9r | |||||||||||||||
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Title | Model of APC/C-CDC20-UBE2C from H2A/H2B-bound complex | |||||||||||||||
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![]() | CELL CYCLE / ubiquitin ligase / histone / chromatin / ubiquitin / complex | |||||||||||||||
Function / homology | ![]() metaphase/anaphase transition of cell cycle / metaphase/anaphase transition of meiosis I / Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components / mitotic checkpoint complex / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of exit from mitosis / regulation of meiotic nuclear division / free ubiquitin chain polymerization / positive regulation of synapse maturation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase ...metaphase/anaphase transition of cell cycle / metaphase/anaphase transition of meiosis I / Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components / mitotic checkpoint complex / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of exit from mitosis / regulation of meiotic nuclear division / 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 / Phosphorylation of Emi1 / 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 / positive regulation of synaptic plasticity / Phosphorylation of the APC/C / regulation of exit from mitosis / anaphase-promoting complex binding / (E3-independent) E2 ubiquitin-conjugating enzyme / positive regulation of mitotic metaphase/anaphase transition / positive regulation of dendrite morphogenesis / ubiquitin ligase activator activity / positive regulation of ubiquitin protein ligase activity / protein K11-linked ubiquitination / regulation of mitotic metaphase/anaphase transition / exit from mitosis / ubiquitin-ubiquitin ligase activity / mitotic sister chromatid cohesion / E2 ubiquitin-conjugating enzyme / mitotic metaphase chromosome alignment / mitotic spindle assembly checkpoint signaling / 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 / mitotic spindle assembly / ubiquitin ligase complex / enzyme-substrate adaptor activity / positive regulation of axon extension / ubiquitin-like ligase-substrate adaptor activity / heterochromatin / protein K48-linked ubiquitination / intercellular bridge / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / Resolution of Sister Chromatid Cohesion / nuclear periphery / regulation of mitotic cell cycle / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / 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 / RHO GTPases Activate Formins / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / brain development / kinetochore / CDK-mediated phosphorylation and removal of Cdc6 / spindle / protein polyubiquitination / spindle pole / neuron projection development / ubiquitin-protein transferase activity / mitotic spindle / Separation of Sister Chromatids / ubiquitin protein ligase activity / Antigen processing: Ubiquitination & Proteasome degradation / nervous system development / mitotic cell cycle / microtubule cytoskeleton / Senescence-Associated Secretory Phenotype (SASP) / ubiquitin-dependent protein catabolic process / protein phosphatase binding / molecular adaptor activity / proteasome-mediated ubiquitin-dependent protein catabolic process / cell differentiation / Ub-specific processing proteases / protein ubiquitination / cell division / negative regulation of gene expression / intracellular membrane-bounded organelle / centrosome / ubiquitin protein ligase binding / nucleolus / zinc ion binding / nucleoplasm / ATP binding / nucleus / plasma membrane Similarity search - Function | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||||||||
![]() | Skrajna, A. / Bodrug, T. / Brown, N.G. / McGinty, R.K. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: APC/C-mediated ubiquitylation of extranucleosomal histone complexes lacking canonical degrons. Authors: Aleksandra Skrajna / Tatyana Bodrug / Raquel C Martinez-Chacin / Caleb B Fisher / Kaeli A Welsh / Holly C Simmons / Eyla C Arteaga / Jake M Simmons / Mohamed A Nasr / Kyle M LaPak / Anh ...Authors: Aleksandra Skrajna / Tatyana Bodrug / Raquel C Martinez-Chacin / Caleb B Fisher / Kaeli A Welsh / Holly C Simmons / Eyla C Arteaga / Jake M Simmons / Mohamed A Nasr / Kyle M LaPak / Anh Nguyen / Mai T Huynh / Isabel Fargo / Joshua G Welfare / Yani Zhao / David S Lawrence / Dennis Goldfarb / Nicholas G Brown / Robert K McGinty / ![]() Abstract: Non-degradative histone ubiquitylation plays a myriad of well-defined roles in the regulation of gene expression and choreographing DNA damage repair pathways. In contrast, the contributions of ...Non-degradative histone ubiquitylation plays a myriad of well-defined roles in the regulation of gene expression and choreographing DNA damage repair pathways. In contrast, the contributions of degradative histone ubiquitylation on genomic processes has remained elusive. Recently, the APC/C has been shown to ubiquitylate histones to regulate gene expression in pluripotent cells, but the molecular mechanism is unclear. Here we show that despite directly binding to the nucleosome through subunit APC3, the APC/C is unable to ubiquitylate nucleosomal histones. In contrast, extranucleosomal H2A/H2B and H3/H4 complexes are broadly ubiquitylated by the APC/C in an unexpected manner. Using a combination of cryo-electron microscopy (cryo-EM) and biophysical and enzymatic assays, we demonstrate that APC8 and histone tails direct APC/C-mediated polyubiquitylation of core histones in the absence of traditional APC/C substrate degron sequences. Taken together, our work implicates APC/C-nucleosome tethering in the degradation of diverse chromatin-associated proteins and extranucleosomal histones for the regulation of transcription and the cell cycle and for preventing toxicity due to excess histone levels. | |||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1.5 MB | Display | ![]() |
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PDB format | ![]() | 1 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.5 MB | Display | |
Data in XML | ![]() | 174.6 KB | Display | |
Data in CIF | ![]() | 297.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 48928MC ![]() 9n9sC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Anaphase-promoting complex subunit ... , 11 types, 13 molecules ACDGWHILMNOYZ
#1: Protein | Mass: 217566.141 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() | ||||||||||||||
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#2: Protein | Mass: 9854.647 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() | ||||||||||||||
#3: Protein | Mass: 6556.302 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() | ||||||||||||||
#4: Protein | Mass: 9920.108 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #5: Protein | | Mass: 6764.688 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #6: Protein | | Mass: 92303.305 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #9: Protein | | Mass: 21310.152 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #10: Protein | | Mass: 8528.309 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #11: Protein | | Mass: 94149.156 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #12: Protein | | Mass: 85445.961 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #16: Protein | Mass: 63204.020 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Cell division cycle protein ... , 4 types, 7 molecules JPKSRUV
#7: Protein | Mass: 92519.547 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #8: Protein | Mass: 71929.656 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #14: Protein | | Mass: 54796.508 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #15: Protein | Mass: 69075.133 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Protein / Non-polymers , 2 types, 5 molecules Q

#13: Protein | Mass: 16346.630 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#17: Chemical | ChemComp-ZN / |
-Details
Has ligand of interest | N |
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Has protein modification | N |
-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
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Molecular weight | Value: 1.2 MDa / Experimental value: YES | ||||||||||||||||||||||||
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Conc.: 1.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE-PROPANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 42 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software | Name: PHENIX / Version: 1.20.1_4487 / Category: model refinement |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 183499 / Symmetry type: POINT |
Refinement | Highest resolution: 3.9 Å Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) |