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Yorodumi- EMDB-4021: Human Anaphase-Promoting Complex/Cyclosome (APC/C) APC15 deletion... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4021 | |||||||||
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Title | Human Anaphase-Promoting Complex/Cyclosome (APC/C) APC15 deletion mutant with Mitotic Checkpoint Complex (MCC) in a closed conformation. | |||||||||
Map data | Human Anaphase-Promoting Complex/Cyclosome (APC/C) APC15 deletion mutant with Mitotic Checkpoint Complex (MCC) in a closed conformation | |||||||||
Sample |
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Function / homology | Function and homology information metaphase/anaphase transition of cell cycle / mitotic spindle assembly checkpoint MAD1-MAD2 complex / 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 mitotic cell cycle spindle assembly checkpoint / establishment of centrosome localization / regulation of meiotic nuclear division / meiotic sister chromatid cohesion, centromeric ...metaphase/anaphase transition of cell cycle / mitotic spindle assembly checkpoint MAD1-MAD2 complex / 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 mitotic cell cycle spindle assembly checkpoint / establishment of centrosome localization / regulation of meiotic nuclear division / meiotic sister chromatid cohesion, centromeric / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / positive regulation of synapse maturation / 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 / regulation of meiotic cell cycle / metaphase/anaphase transition of mitotic cell cycle / anaphase-promoting complex-dependent catabolic process / positive regulation of synaptic plasticity / regulation of exit from mitosis / anaphase-promoting complex binding / nuclear pore nuclear basket / outer kinetochore / Phosphorylation of the APC/C / protein localization to chromosome, centromeric region / positive regulation of mitotic metaphase/anaphase transition / positive regulation of ubiquitin protein ligase activity / ubiquitin ligase activator activity / Regulation of APC/C activators between G1/S and early anaphase / protein K11-linked ubiquitination / enzyme-substrate adaptor activity / positive regulation of dendrite morphogenesis / regulation of mitotic metaphase/anaphase transition / negative regulation of mitotic cell cycle / ubiquitin-ubiquitin ligase activity / mitotic sister chromatid cohesion / negative regulation of ubiquitin protein ligase activity / mitotic metaphase chromosome alignment / mitotic spindle assembly checkpoint signaling / regulation of mitotic cell cycle / establishment of mitotic spindle orientation / mitotic sister chromatid segregation / cullin family protein binding / Transcriptional Regulation by VENTX / ubiquitin-like ligase-substrate adaptor activity / mitotic spindle assembly / positive regulation of axon extension / protein K48-linked ubiquitination / heterochromatin / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Resolution of Sister Chromatid Cohesion / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / nuclear periphery / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / SCF-beta-TrCP mediated degradation of Emi1 / negative regulation of protein catabolic process / Assembly of the pre-replicative complex / RHO GTPases Activate Formins / CDK-mediated phosphorylation and removal of Cdc6 / 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 / mitotic spindle / kinetochore / spindle pole / spindle / Separation of Sister Chromatids / ubiquitin-protein transferase activity / microtubule cytoskeleton / ubiquitin protein ligase activity / Antigen processing: Ubiquitination & Proteasome degradation / Senescence-Associated Secretory Phenotype (SASP) / mitotic cell cycle / nervous system development / protein phosphatase binding / ubiquitin-dependent protein catabolic process / cell differentiation / molecular adaptor activity / non-specific serine/threonine protein kinase / protein kinase activity / Ub-specific processing proteases / protein ubiquitination / cell division / negative regulation of gene expression / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / ubiquitin protein ligase binding / negative regulation of apoptotic process / nucleolus / apoptotic process / perinuclear region of cytoplasm / protein homodimerization activity / zinc ion binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.8 Å | |||||||||
Authors | Stark H / Schulman B / Peters JM | |||||||||
Citation | Journal: Mol Cell / Year: 2016 Title: Cryo-EM of Mitotic Checkpoint Complex-Bound APC/C Reveals Reciprocal and Conformational Regulation of Ubiquitin Ligation. Authors: Masaya Yamaguchi / Ryan VanderLinden / Florian Weissmann / Renping Qiao / Prakash Dube / Nicholas G Brown / David Haselbach / Wei Zhang / Sachdev S Sidhu / Jan-Michael Peters / Holger Stark ...Authors: Masaya Yamaguchi / Ryan VanderLinden / Florian Weissmann / Renping Qiao / Prakash Dube / Nicholas G Brown / David Haselbach / Wei Zhang / Sachdev S Sidhu / Jan-Michael Peters / Holger Stark / Brenda A Schulman / Abstract: The mitotic checkpoint complex (MCC) coordinates proper chromosome biorientation on the spindle with ubiquitination activities of CDC20-activated anaphase-promoting complex/cyclosome (APC/C(CDC20)). ...The mitotic checkpoint complex (MCC) coordinates proper chromosome biorientation on the spindle with ubiquitination activities of CDC20-activated anaphase-promoting complex/cyclosome (APC/C(CDC20)). APC/C(CDC20) and two E2s, UBE2C and UBE2S, catalyze ubiquitination through distinct architectures for linking ubiquitin (UB) to substrates and elongating polyUB chains, respectively. MCC, which contains a second molecule of CDC20, blocks APC/C(CDC20)-UBE2C-dependent ubiquitination of Securin and Cyclins, while differentially determining or inhibiting CDC20 ubiquitination to regulate spindle surveillance, checkpoint activation, and checkpoint termination. Here electron microscopy reveals conformational variation of APC/C(CDC20)-MCC underlying this multifaceted regulation. MCC binds APC/C-bound CDC20 to inhibit substrate access. However, rotation about the CDC20-MCC assembly and conformational variability of APC/C modulate UBE2C-catalyzed ubiquitination of MCC's CDC20 molecule. Access of UBE2C is limiting for subsequent polyubiquitination by UBE2S. We propose that conformational dynamics of APC/C(CDC20)-MCC modulate E2 activation and determine distinctive ubiquitination activities as part of a response mechanism ensuring accurate sister chromatid segregation. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_4021.map.gz | 116.3 MB | EMDB map data format | |
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Header (meta data) | emd-4021-v30.xml emd-4021.xml | 11.9 KB 11.9 KB | Display Display | EMDB header |
Images | emd_4021.png | 206 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4021 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4021 | HTTPS FTP |
-Validation report
Summary document | emd_4021_validation.pdf.gz | 372.7 KB | Display | EMDB validaton report |
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Full document | emd_4021_full_validation.pdf.gz | 372.3 KB | Display | |
Data in XML | emd_4021_validation.xml.gz | 6.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4021 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4021 | HTTPS FTP |
-Related structure data
Related structure data | 5khuMC 4022C 4023C 4024C 4025C 4026C 4027C 4028C 5khrC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_4021.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Human Anaphase-Promoting Complex/Cyclosome (APC/C) APC15 deletion mutant with Mitotic Checkpoint Complex (MCC) in a closed conformation | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.27 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Human Anaphase-Promoting Complex/Cyclosome (APC/C) APC15 deletion...
Entire | Name: Human Anaphase-Promoting Complex/Cyclosome (APC/C) APC15 deletion mutant with Mitotic Checkpoint Complex (MCC) in a closed conformation. |
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Components |
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-Supramolecule #1: Human Anaphase-Promoting Complex/Cyclosome (APC/C) APC15 deletion...
Supramolecule | Name: Human Anaphase-Promoting Complex/Cyclosome (APC/C) APC15 deletion mutant with Mitotic Checkpoint Complex (MCC) in a closed conformation. type: complex / ID: 1 / Parent: 0 Details: Human Anaphase-Promoting Complex/Cyclosome (APC/C) APC15 deletion mutant with Mitotic Checkpoint Complex (MCC) in a closed conformation. |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) / Recombinant plasmid: biGBac |
Molecular weight | Theoretical: 1.5 MDa |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.1 mg/mL | ||||||||||||
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Buffer | pH: 8 Component:
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV | ||||||||||||
Details | Grafix treated complex |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON II (4k x 4k) / Detector mode: INTEGRATING / Digitization - Frames/image: 2-17 / Number grids imaged: 1 / Number real images: 5911 / Average exposure time: 1.0 sec. / Average electron dose: 2.35 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated defocus max: 0.0035 µm / Calibrated defocus min: 0.0007 µm / Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Cs: 0.001 mm / Nominal magnification: 94000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |