4GGC

Structural Analysis of Human Cdc20 Supports Multi-site Degron Recognition by APC/C


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.35 Å
  • R-Value Free: 0.146 
  • R-Value Work: 0.132 
  • R-Value Observed: 0.133 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural analysis of human Cdc20 supports multisite degron recognition by APC/C.

Tian, W.Li, B.Warrington, R.Tomchick, D.R.Yu, H.Luo, X.

(2012) Proc Natl Acad Sci U S A 109: 18419-18424

  • DOI: https://doi.org/10.1073/pnas.1213438109
  • Primary Citation of Related Structures:  
    4GGA, 4GGC, 4GGD

  • PubMed Abstract: 

    The anaphase-promoting complex/cyclosome (APC/C) promotes anaphase onset and mitotic exit through ubiquitinating securin and cyclin B1. The mitotic APC/C activator, the cell division cycle 20 (Cdc20) protein, directly interacts with APC/C degrons--the destruction (D) and KEN boxes. APC/C(Cdc20) is the target of the spindle checkpoint. Checkpoint inhibition of APC/C(Cdc20) requires the binding of a BubR1 KEN box to Cdc20. How APC/C recognizes substrates is not understood. We report the crystal structures of human Cdc20 alone or bound to a BubR1 KEN box. Cdc20 has a disordered N-terminal region and a C-terminal WD40 β propeller with a preformed KEN-box-binding site at its top face. We identify a second conserved surface at the side of the Cdc20 β propeller as a D-box-binding site. The D box of securin, but not its KEN box, is critical for securin ubiquitination by APC/C(Cdc20). Although both motifs contribute to securin ubiquitination by APC/C(Cdh1), securin mutants lacking either motif are efficiently ubiquitinated. Furthermore, D-box peptides diminish the ubiquitination of KEN-box substrates by APC/C(Cdh1), suggesting possible competition between the two motifs. Our results indicate the lack of strong positive cooperativity between the two degrons of securin. We propose that low-cooperativity, multisite target recognition enables APC/C to robustly ubiquitinate diverse substrates and helps to drive cell cycle oscillations.


  • Organizational Affiliation

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cell division cycle protein 20 homolog318Homo sapiensMutation(s): 0 
Gene Names: CDC20
UniProt & NIH Common Fund Data Resources
Find proteins for Q12834 (Homo sapiens)
Explore Q12834 
Go to UniProtKB:  Q12834
PHAROS:  Q12834
GTEx:  ENSG00000117399 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ12834
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.35 Å
  • R-Value Free: 0.146 
  • R-Value Work: 0.132 
  • R-Value Observed: 0.133 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.281α = 90
b = 86.933β = 112.97
c = 48.339γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-3000data collection
HKL-3000data reduction
HKL-3000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-11-07
    Type: Initial release
  • Version 1.1: 2012-12-26
    Changes: Database references
  • Version 1.2: 2017-11-15
    Changes: Refinement description
  • Version 1.3: 2024-02-28
    Changes: Data collection, Database references, Derived calculations