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Yorodumi- PDB-9gaw: High-resolution structure of the Anaphase-promoting complex/cyclo... -
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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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Keywords | CELL CYCLE / APC/C / cyclosome / Cdc20 / Cdh1 / ubiquitination / Emi1 / mitosis | |||||||||
| Function / homology | Function and homology informationnegative regulation of DNA endoreduplication / positive regulation of biomineral tissue development / negative regulation of meiotic nuclear division / positive regulation of mesenchymal stem cell migration / positive regulation of anaphase-promoting complex-dependent catabolic process / negative regulation of mitotic metaphase/anaphase transition / Mitotic Metaphase/Anaphase Transition / negative regulation of ubiquitin-protein transferase activity / positive regulation of synapse maturation / regulation of meiotic nuclear division ...negative regulation of DNA endoreduplication / positive regulation of biomineral tissue development / negative regulation of meiotic nuclear division / positive regulation of mesenchymal stem cell migration / positive regulation of anaphase-promoting complex-dependent catabolic process / negative regulation of mitotic metaphase/anaphase transition / Mitotic Metaphase/Anaphase Transition / negative regulation of ubiquitin-protein transferase activity / positive regulation of synapse maturation / 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 / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / positive regulation of synaptic plasticity / Phosphorylation of Emi1 / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / vesicle organization / regulation of meiotic cell cycle / anaphase-promoting complex-dependent catabolic process / metaphase/anaphase transition of mitotic cell cycle / protein branched polyubiquitination / lens fiber cell differentiation / Phosphorylation of the APC/C / anaphase-promoting complex binding / regulation of exit from mitosis / positive regulation of dendrite morphogenesis / spindle assembly involved in female meiosis I / positive regulation of mitotic metaphase/anaphase transition / positive regulation of ubiquitin protein ligase activity / ubiquitin ligase activator activity / protein K11-linked ubiquitination / oocyte maturation / meiotic spindle / regulation of mitotic metaphase/anaphase transition / ubiquitin-ubiquitin ligase activity / molecular function inhibitor activity / negative regulation of ubiquitin protein ligase activity / mitotic metaphase chromosome alignment / regulation of mitotic nuclear division / 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 / positive regulation of G2/M transition of mitotic cell cycle / enzyme-substrate adaptor activity / positive regulation of osteoblast differentiation / positive regulation of axon extension / ubiquitin-like ligase-substrate adaptor activity / protein K48-linked ubiquitination / heterochromatin / Cyclin A:Cdk2-associated events at S phase entry / intercellular bridge / 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 / G protein-coupled receptor binding / 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 / nuclear membrane / molecular adaptor activity / cell differentiation / protein ubiquitination / negative regulation of gene expression / cell division / DNA repair / intracellular membrane-bounded organelle / positive regulation of cell population proliferation / DNA damage response / ubiquitin protein ligase binding / centrosome / protein kinase binding / nucleolus Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | Hoefler, A. / Yu, J. / Chang, L. / Zhang, Z. / Yang, J. / Boland, A. / Barford, D. | |||||||||
| Funding support | Switzerland, United Kingdom, 2items
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Citation | Journal: Nat Commun / Year: 2024Title: 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. | |||||||||
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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 | 9gaw.cif.gz | 1.6 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb9gaw.ent.gz | 1.3 MB | Display | PDB format |
| PDBx/mmJSON format | 9gaw.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 9gaw_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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| Full document | 9gaw_full_validation.pdf.gz | 1.5 MB | Display | |
| Data in XML | 9gaw_validation.xml.gz | 213.1 KB | Display | |
| Data in CIF | 9gaw_validation.cif.gz | 329.8 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ga/9gaw ftp://data.pdbj.org/pub/pdb/validation_reports/ga/9gaw | HTTPS FTP |
-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 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 LDANIOGWMHYZC
| #1: Protein | Mass: 21282.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC10, APC10 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9UM13 | ||||||||
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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.) Homo sapiens (human) / Gene: ANAPC15, C11orf51, HSPC020 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P60006 | ||||||||
| #3: Protein | Mass: 216725.469 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC1, TSG24 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9H1A4 | ||||||||
| #4: Protein | Mass: 93938.977 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: Trichoplusia ni (cabbage looper) / References: UniProt: Q9UJX6 | ||||||||
| #5: Protein | Mass: 93014.070 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC4, APC4 / Production host: Trichoplusia ni (cabbage looper) / Strain (production host): ANAPC4 / References: UniProt: Q9UJX5 | ||||||||
| #6: Protein | Mass: 85179.766 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC5, APC5 / Production host: Trichoplusia ni (cabbage looper) / Strain (production host): APC4 / References: UniProt: Q9UJX4 | ||||||||
| #9: Protein | Mass: 9793.999 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDC26, ANAPC12, C9orf17 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q8NHZ8#10: 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: Trichoplusia ni (cabbage looper) / References: UniProt: Q9BS18#11: Protein | | Mass: 11677.995 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: Trichoplusia ni (cabbage looper) / References: UniProt: Q96DE5#13: Protein | Mass: 66929.367 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ANAPC7, APC7 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9UJX3#16: 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: Trichoplusia ni (cabbage looper) / References: UniProt: Q9NYG5 |
-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.) Homo sapiens (human) / Gene: FBXO5, EMI1, FBX5 / 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, CDH1, FYR, FZR, KIAA1242 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9UM11 |
-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.) Homo sapiens (human) / Gene: CDC16, ANAPC6 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q13042#12: Protein | Mass: 91973.125 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: Trichoplusia ni (cabbage looper) / References: UniProt: P30260#14: Protein | Mass: 68921.031 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDC23, ANAPC8 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9UJX2 |
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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: Homo sapiens (human) | ||||||||||||||||||||
| Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) | ||||||||||||||||||||
| Buffer solution | pH: 8 | ||||||||||||||||||||
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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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| 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
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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 |
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About Yorodumi



Homo sapiens (human)
Switzerland,
United Kingdom, 2items
Citation







PDBj




















Trichoplusia ni (cabbage looper)

FIELD EMISSION GUN
