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- EMDB-51190: High-resolution structure of the Anaphase-promoting complex/cyclo... -
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Basic information
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Title | High-resolution structure of the Anaphase-promoting complex/cyclosome (APC/C) bound to co-activator Cdh1 | |||||||||
![]() | Composite map (unsharpened) of the Anaphase-promoting complex/cyclosome (APC/C) bound to co-factor Cdh1 | |||||||||
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![]() | APC/C / cyclosome / Cdc20 / Cdh1 / ubiquitination / Emi1 / mitosis / Cell cycle | |||||||||
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 | 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
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Downloads & links
-EMDB archive
Map data | ![]() | 88.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 41.4 KB 41.4 KB | Display Display | ![]() |
Images | ![]() | 73.5 KB | ||
Filedesc metadata | ![]() | 13.5 KB | ||
Others | ![]() | 5.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9gawMC ![]() 8pkpC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||
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Annotation | Composite map (unsharpened) of the Anaphase-promoting complex/cyclosome (APC/C) bound to co-factor Cdh1 | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size |
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Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : Anaphase-promoting complex (APC/C) bound to co-activator Cdh1
+Supramolecule #1: Anaphase-promoting complex (APC/C) bound to co-activator Cdh1
+Macromolecule #1: Anaphase-promoting complex subunit 10
+Macromolecule #2: Anaphase-promoting complex subunit 15
+Macromolecule #3: Anaphase-promoting complex subunit 1
+Macromolecule #4: Anaphase-promoting complex subunit 2
+Macromolecule #5: Anaphase-promoting complex subunit 4
+Macromolecule #6: Anaphase-promoting complex subunit 5
+Macromolecule #7: F-box only protein 5
+Macromolecule #8: Cell division cycle protein 16 homolog
+Macromolecule #9: Anaphase-promoting complex subunit CDC26
+Macromolecule #10: Anaphase-promoting complex subunit 13
+Macromolecule #11: Anaphase-promoting complex subunit 16
+Macromolecule #12: Cell division cycle protein 27 homolog
+Macromolecule #13: Anaphase-promoting complex subunit 7
+Macromolecule #14: Cell division cycle protein 23 homolog
+Macromolecule #15: Fizzy-related protein homolog
+Macromolecule #16: Anaphase-promoting complex subunit 11
+Macromolecule #17: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.1 mg/mL | ||||||||||||
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Buffer | pH: 8 Component:
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Grid | Model: Quantifoil R2/2 / Material: COPPER / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 50 | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK III |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Number real images: 8297 / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.5 µm / Nominal defocus min: 1.5 µm |
Sample stage | Specimen holder model: OTHER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |