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- PDB-6q6g: Cryo-EM structure of the APC/C-Cdc20-Cdk2-cyclinA2-Cks2 complex, ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 6q6g | |||||||||
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Title | Cryo-EM structure of the APC/C-Cdc20-Cdk2-cyclinA2-Cks2 complex, the D1 box class | |||||||||
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![]() | CELL CYCLE / spindle assembly checkpoint / anaphase-promoting complex / cyclin / ubiquitination | |||||||||
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 / 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 / positive regulation of synapse maturation / Inactivation of APC/C via direct inhibition of the APC/C complex ...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 / 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 / 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 / Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes / cyclin A2-CDK1 complex / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / cell cycle G1/S phase transition / regulation of meiotic cell cycle / cellular response to luteinizing hormone stimulus / metaphase/anaphase transition of mitotic cell cycle / anaphase-promoting complex-dependent catabolic process / positive regulation of synaptic plasticity / regulation of exit from mitosis / Phosphorylation of the APC/C / anaphase-promoting complex binding / mitotic cell cycle phase transition / ubiquitin ligase activator activity / positive regulation of mitotic metaphase/anaphase transition / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / positive regulation of ubiquitin protein ligase activity / protein K11-linked ubiquitination / cellular response to leptin stimulus / male pronucleus / enzyme-substrate adaptor activity / female pronucleus / regulation of mitotic metaphase/anaphase transition / cellular response to cocaine / response to glucagon / positive regulation of dendrite morphogenesis / ubiquitin-ubiquitin ligase activity / cyclin-dependent protein serine/threonine kinase regulator activity / cellular response to insulin-like growth factor stimulus / mitotic sister chromatid cohesion / mitotic metaphase chromosome alignment / positive regulation of DNA biosynthetic process / cochlea development / cellular response to platelet-derived growth factor stimulus / mitotic spindle assembly checkpoint signaling / cyclin A2-CDK2 complex / G2 Phase / p53-Dependent G1 DNA Damage Response / regulation of DNA replication / Regulation of APC/C activators between G1/S and early anaphase / cullin family protein binding / Telomere Extension By Telomerase / G0 and Early G1 / ubiquitin-like ligase-substrate adaptor activity / Transcriptional Regulation by VENTX / mitotic spindle assembly / cellular response to nitric oxide / cyclin-dependent protein kinase holoenzyme complex / positive regulation of axon extension / animal organ regeneration / heterochromatin / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / Cyclin A/B1/B2 associated events during G2/M transition / Cyclin A:Cdk2-associated events at S phase entry / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Resolution of Sister Chromatid Cohesion / regulation of mitotic cell cycle / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / nuclear periphery / post-translational protein modification / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / SCF-beta-TrCP mediated degradation of Emi1 / cellular response to estradiol stimulus / Assembly of the pre-replicative complex / RHO GTPases Activate Formins / 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 / DNA Damage/Telomere Stress Induced Senescence / brain development / CDK-mediated phosphorylation and removal of Cdc6 / mitotic spindle / kinetochore / SCF(Skp2)-mediated degradation of p27/p21 / spindle pole / spindle / Orc1 removal from chromatin / G1/S transition of mitotic cell cycle / Separation of Sister Chromatids / ubiquitin-protein transferase activity / G2/M transition of mitotic cell cycle / microtubule cytoskeleton / ubiquitin protein ligase activity / positive regulation of fibroblast proliferation Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Zhang, S. / Barford, D. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C. Authors: Suyang Zhang / Thomas Tischer / David Barford / ![]() ![]() Abstract: The anaphase-promoting complex/cyclosome (APC/C) orchestrates cell cycle progression by controlling the temporal degradation of specific cell cycle regulators. Although cyclin A2 and cyclin B1 are ...The anaphase-promoting complex/cyclosome (APC/C) orchestrates cell cycle progression by controlling the temporal degradation of specific cell cycle regulators. Although cyclin A2 and cyclin B1 are both targeted for degradation by the APC/C, during the spindle assembly checkpoint (SAC), the mitotic checkpoint complex (MCC) represses APC/C's activity towards cyclin B1, but not cyclin A2. Through structural, biochemical and in vivo analysis, we identify a non-canonical D box (D2) that is critical for cyclin A2 ubiquitination in vitro and degradation in vivo. During the SAC, cyclin A2 is ubiquitinated by the repressed APC/C-MCC, mediated by the cooperative engagement of its KEN and D2 boxes, ABBA motif, and the cofactor Cks. Once the SAC is satisfied, cyclin A2 binds APC/C-Cdc20 through two mutually exclusive binding modes, resulting in differential ubiquitination efficiency. Our findings reveal that a single substrate can engage an E3 ligase through multiple binding modes, affecting its degradation timing and efficiency. | |||||||||
History |
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Structure visualization
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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 | ![]() | 1.2 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 | ![]() | 214.2 KB | Display | |
Data in CIF | ![]() | 335 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4465MC ![]() 4463C ![]() 4464C ![]() 4466C ![]() 4467C ![]() 6q6hC C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Cell division cycle protein ... , 4 types, 7 molecules RKQJPUV
#1: Protein | Mass: 54796.508 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||
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#9: Protein | Mass: 71747.516 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #14: Protein | Mass: 91973.125 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #16: Protein | Mass: 68921.031 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Protein , 1 types, 1 molecules S
#2: Protein | Mass: 44944.344 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Anaphase-promoting complex subunit ... , 11 types, 13 molecules LDANIOCGWMHYZ
#3: Protein | Mass: 21282.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||
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#4: Protein | Mass: 14286.727 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||
#5: Protein | Mass: 207282.328 Da / Num. of mol.: 1 Mutation: deletion of residues 307-395,deletion of residues 307-395 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||
#6: Protein | Mass: 93938.977 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||
#7: Protein | Mass: 92219.227 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||
#8: Protein | Mass: 85179.766 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||
#10: Protein | Mass: 9854.647 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||||||
#11: Protein | Mass: 9793.999 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #12: Protein | | Mass: 8528.309 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #13: Protein | | Mass: 11677.995 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #15: Protein | Mass: 66929.367 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-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: 1.3 MDa | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 / Details: 20mM Hepes, 150mM NaCl, 0.5mM TCEP | ||||||||||||||||||||||||
Specimen | Conc.: 0.15 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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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 |
Image recording | Electron dose: 28 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
EM software | Name: RELION / Version: 3 / Category: 3D reconstruction |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 176826 / Symmetry type: POINT |