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- PDB-9gaw: High-resolution structure of the Anaphase-promoting complex/cyclo... -
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Open data
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Basic information
Entry | Database: PDB / ID: 9gaw | |||||||||
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Title | High-resolution structure of the Anaphase-promoting complex/cyclosome (APC/C) bound to co-activator Cdh1 | |||||||||
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![]() | CELL CYCLE / APC/C / cyclosome / Cdc20 / Cdh1 / ubiquitination / Emi1 / mitosis | |||||||||
Function / homology | ![]() negative regulation of DNA endoreduplication / positive regulation of biomineral tissue development / negative regulation of meiotic nuclear division / negative regulation of mitotic metaphase/anaphase transition / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of mesenchymal stem cell migration / Mitotic Metaphase/Anaphase Transition / regulation of meiotic nuclear division / negative regulation of ubiquitin-protein transferase activity / positive regulation of synapse maturation ...negative regulation of DNA endoreduplication / positive regulation of biomineral tissue development / negative regulation of meiotic nuclear division / negative regulation of mitotic metaphase/anaphase transition / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of mesenchymal stem cell migration / Mitotic Metaphase/Anaphase Transition / regulation of meiotic nuclear division / negative regulation of ubiquitin-protein transferase activity / 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 / vesicle organization / 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 / positive regulation of synaptic plasticity / Phosphorylation of the APC/C / regulation of exit from mitosis / anaphase-promoting complex binding / positive regulation of mitotic metaphase/anaphase transition / positive regulation of dendrite morphogenesis / spindle assembly involved in female meiosis I / ubiquitin ligase activator activity / positive regulation of ubiquitin protein ligase activity / protein K11-linked ubiquitination / meiotic spindle / oocyte maturation / regulation of mitotic metaphase/anaphase transition / ubiquitin-ubiquitin ligase activity / regulation of mitotic nuclear division / molecular function inhibitor activity / mitotic metaphase chromosome alignment / negative regulation of ubiquitin protein ligase activity / G1/S-Specific Transcription / mitotic G2 DNA damage checkpoint signaling / microtubule polymerization / Regulation of APC/C activators between G1/S and early anaphase / regulation of DNA replication / cullin family protein binding / Transcriptional Regulation by VENTX / negative regulation of cellular senescence / ubiquitin ligase inhibitor activity / enzyme-substrate adaptor activity / positive regulation of axon extension / ubiquitin-like ligase-substrate adaptor activity / positive regulation of osteoblast differentiation / heterochromatin / protein K48-linked ubiquitination / intercellular bridge / Cyclin A:Cdk2-associated events at S phase entry / positive regulation of G2/M transition of mitotic cell cycle / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / nuclear periphery / regulation 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 / brain development / kinetochore / CDK-mediated phosphorylation and removal of Cdc6 / spindle / 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 / nuclear membrane / cell differentiation / protein ubiquitination / cell division / negative regulation of gene expression / DNA repair / intracellular membrane-bounded organelle / positive regulation of cell population proliferation / centrosome / ubiquitin protein ligase binding / DNA damage response / protein kinase binding / nucleolus / zinc ion binding Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
![]() | Hoefler, A. / Yu, J. / Chang, L. / Zhang, Z. / Yang, J. / Boland, A. / Barford, D. | |||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Cryo-EM structures of apo-APC/C and APC/C complexes provide insights into APC/C regulation. Authors: Anna Höfler / Jun Yu / Jing Yang / Ziguo Zhang / Leifu Chang / Stephen H McLaughlin / Geoffrey W Grime / Elspeth F Garman / Andreas Boland / David Barford / ![]() ![]() Abstract: APC/C is a multi-subunit complex that functions as a master regulator of cell division. It controls progression through the cell cycle by timely marking mitotic cyclins and other cell cycle ...APC/C is a multi-subunit complex that functions as a master regulator of cell division. It controls progression through the cell cycle by timely marking mitotic cyclins and other cell cycle regulatory proteins for degradation. The APC/C itself is regulated by the sequential action of its coactivator subunits CDC20 and CDH1, post-translational modifications, and its inhibitory binding partners EMI1 and the mitotic checkpoint complex. In this study, we took advantage of developments in cryo-electron microscopy to determine the structures of human APC/C and apo-APC/C at 2.9 Å and 3.2 Å resolution, respectively, providing insights into the regulation of APC/C activity. The high-resolution maps allow the unambiguous assignment of an α-helix to the N-terminus of CDH1 (CDH1) in the APC/C ternary complex. We also identify a zinc-binding module in APC2 that confers structural stability to the complex, and we confirm the presence of zinc ions experimentally. Finally, due to the higher resolution and well defined density of these maps, we are able to build, aided by AlphaFold predictions, several intrinsically disordered regions in different APC/C subunits that likely play a role in proper APC/C assembly and regulation of its activity. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 1.6 MB | Display | ![]() |
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PDB format | ![]() | 1.3 MB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 13931MC ![]() 19711MC ![]() 51190MC ![]() 8pkpC 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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Components
-Anaphase-promoting complex subunit ... , 11 types, 13 molecules LDANIOGWMHYZC
#1: Protein | Mass: 21282.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||||
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#2: Protein | Mass: 14286.727 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||||
#3: Protein | Mass: 216725.469 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||||
#4: Protein | Mass: 93938.977 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||||
#5: Protein | Mass: 93014.070 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||||
#6: Protein | Mass: 85179.766 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||||
#9: Protein | Mass: 9793.999 Da / Num. of mol.: 2 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: 11677.995 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #13: Protein | Mass: 66929.367 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #16: Protein | | Mass: 9854.647 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Protein , 2 types, 2 molecules SR
#7: Protein | Mass: 50227.488 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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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.) ![]() ![]() |
-Cell division cycle protein ... , 3 types, 6 molecules KQJPUV
#8: Protein | Mass: 71747.516 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #12: Protein | Mass: 91973.125 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #14: Protein | Mass: 68921.031 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Non-polymers , 1 types, 6 molecules 
#17: Chemical | ChemComp-ZN / |
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-Details
Has ligand of interest | Y |
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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
Component | Name: Anaphase-promoting complex (APC/C) bound to co-activator Cdh1 Type: COMPLEX / Entity ID: #1-#14 / Source: RECOMBINANT | ||||||||||||||||||||
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Molecular weight | Value: 1.2 MDa / Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: ![]() | ||||||||||||||||||||
Source (recombinant) | Organism: ![]() | ||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid type: Quantifoil R2/2 | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3500 nm / Nominal defocus min: 1500 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: OTHER |
Image recording | Electron dose: 40 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON III (4k x 4k) / Num. of real images: 8297 |
Image scans | Width: 4096 / Height: 4096 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1800000 / Details: The particles were automatically selected | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 364331 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | B value: 80 / Protocol: RIGID BODY FIT / Space: REAL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 4UI9 Accession code: 4UI9 / Source name: PDB / Type: experimental model |