6Q6G

Cryo-EM structure of the APC/C-Cdc20-Cdk2-cyclinA2-Cks2 complex, the D1 box class


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.20 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C.

Zhang, S.Tischer, T.Barford, D.

(2019) Nat Commun 10: 3863-3863

  • DOI: https://doi.org/10.1038/s41467-019-11833-2
  • Primary Citation of Related Structures:  
    6Q6G, 6Q6H

  • PubMed 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 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.


  • Organizational Affiliation

    MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division cycle protein 20 homologA [auth R]499Homo sapiensMutation(s): 0 
Gene Names: CDC20
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Find proteins for Q12834 (Homo sapiens)
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PHAROS:  Q12834
GTEx:  ENSG00000117399 
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UniProt GroupQ12834
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Cyclin-A2B [auth S]400Homo sapiensMutation(s): 0 
Gene Names: CCNA2CCN1CCNA
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Find proteins for P20248 (Homo sapiens)
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PHAROS:  P20248
GTEx:  ENSG00000145386 
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UniProt GroupP20248
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Anaphase-promoting complex subunit 10C [auth L]185Homo sapiensMutation(s): 0 
Gene Names: ANAPC10APC10
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PHAROS:  Q9UM13
GTEx:  ENSG00000164162 
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UniProt GroupQ9UM13
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Anaphase-promoting complex subunit 15121Homo sapiensMutation(s): 0 
Gene Names: ANAPC15C11orf51HSPC020
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Find proteins for P60006 (Homo sapiens)
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GTEx:  ENSG00000110200 
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UniProt GroupP60006
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
Anaphase-promoting complex subunit 1,Anaphase-promoting complex subunit 1E [auth A]1,855Homo sapiensMutation(s): 0 
Gene Names: ANAPC1TSG24
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GTEx:  ENSG00000153107 
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UniProt GroupQ9H1A4
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Entity ID: 6
MoleculeChains Sequence LengthOrganismDetailsImage
Anaphase-promoting complex subunit 2F [auth N]822Homo sapiensMutation(s): 0 
Gene Names: ANAPC2APC2KIAA1406
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PHAROS:  Q9UJX6
GTEx:  ENSG00000176248 
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UniProt GroupQ9UJX6
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Entity ID: 7
MoleculeChains Sequence LengthOrganismDetailsImage
Anaphase-promoting complex subunit 4G [auth I]808Homo sapiensMutation(s): 0 
Gene Names: ANAPC4APC4
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PHAROS:  Q9UJX5
GTEx:  ENSG00000053900 
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UniProt GroupQ9UJX5
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Entity ID: 8
MoleculeChains Sequence LengthOrganismDetailsImage
Anaphase-promoting complex subunit 5H [auth O]755Homo sapiensMutation(s): 0 
Gene Names: ANAPC5APC5
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GTEx:  ENSG00000089053 
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Entity ID: 9
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division cycle protein 16 homologI [auth K],
Q
620Homo sapiensMutation(s): 0 
Gene Names: CDC16ANAPC6
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GTEx:  ENSG00000130177 
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Entity ID: 10
MoleculeChains Sequence LengthOrganismDetailsImage
Anaphase-promoting complex subunit 11J [auth C]84Homo sapiensMutation(s): 0 
Gene Names: ANAPC11HSPC214
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GTEx:  ENSG00000141552 
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Entity ID: 11
MoleculeChains Sequence LengthOrganismDetailsImage
Anaphase-promoting complex subunit CDC26K [auth G],
L [auth W]
85Homo sapiensMutation(s): 0 
Gene Names: CDC26ANAPC12C9orf17
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GTEx:  ENSG00000176386 
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Entity ID: 12
MoleculeChains Sequence LengthOrganismDetailsImage
Anaphase-promoting complex subunit 1374Homo sapiensMutation(s): 0 
Gene Names: ANAPC13
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GTEx:  ENSG00000129055 
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UniProt GroupQ9BS18
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Entity ID: 13
MoleculeChains Sequence LengthOrganismDetailsImage
Anaphase-promoting complex subunit 16N [auth H]110Homo sapiensMutation(s): 0 
Gene Names: ANAPC16C10orf104CENP-27
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GTEx:  ENSG00000166295 
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UniProt GroupQ96DE5
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Entity ID: 14
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division cycle protein 27 homologO [auth J],
P
824Homo sapiensMutation(s): 0 
Gene Names: CDC27ANAPC3D0S1430ED17S978E
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Find proteins for P30260 (Homo sapiens)
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GTEx:  ENSG00000004897 
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Entity ID: 15
MoleculeChains Sequence LengthOrganismDetailsImage
Anaphase-promoting complex subunit 7R [auth Y],
U [auth Z]
599Homo sapiensMutation(s): 0 
Gene Names: ANAPC7APC7
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Find proteins for Q9UJX3 (Homo sapiens)
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GTEx:  ENSG00000196510 
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Entity ID: 16
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division cycle protein 23 homologS [auth U],
T [auth V]
597Homo sapiensMutation(s): 0 
Gene Names: CDC23ANAPC8
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Find proteins for Q9UJX2 (Homo sapiens)
Explore Q9UJX2 
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PHAROS:  Q9UJX2
GTEx:  ENSG00000094880 
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UniProt GroupQ9UJX2
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Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.20 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONRELION3.0

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Medical Research Council (United Kingdom)United KingdomMC_UP_1021/6
Cancer Research UKUnited KingdomC576/A14109

Revision History  (Full details and data files)

  • Version 1.0: 2019-09-11
    Type: Initial release
  • Version 1.1: 2024-05-15
    Changes: Data collection, Database references