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Analysis of activator-binding sites on the APC/C supports a cooperative substrate-binding mechanism.

The anaphase-promoting complex or cyclosome (APC/C) is a ubiquitin ligase essential for the completion of mitosis in all eukaryotic cells. Substrates are recruited to the APC/C by activator proteins (Cdc20 or Cdh1), but it is not known where substrates are bound during catalysis. We explored this problem by analyzing mutations in the tetratricopeptide-repeat-containing APC/C subunits. We identified residues in Cdc23 and Cdc27 that are required for APC/C binding to Cdc20 and Cdh1 and for APC/C function in vivo. Mutation of these sites increased the rate of activator dissociation from the APC/C but did not affect reaction processivity, suggesting that the mutations have little effect on substrate dissociation from the active site. Further studies revealed that activator dissociation from the APC/C is inhibited by substrate, and that substrates are not bound solely to activator during catalysis but interact bivalently with an additional binding site on the APC/C core.

Pubmed ID: 19362536


  • Matyskiela ME
  • Morgan DO


Molecular cell

Publication Data

April 10, 2009

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM053270
  • Agency: NIGMS NIH HHS, Id: R01 GM053270
  • Agency: NIGMS NIH HHS, Id: R01 GM053270-19

Mesh Terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Anaphase-Promoting Complex-Cyclosome
  • Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Binding Sites
  • Cdc20 Proteins
  • Cdh1 Proteins
  • Cell Cycle Proteins
  • Enzyme Activation
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Sequence Analysis, Protein
  • Ubiquitin-Protein Ligase Complexes