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Structural organization of the anaphase-promoting complex bound to the mitotic activator Slp1.

Molecular cell | Dec 14, 2007

http://www.ncbi.nlm.nih.gov/pubmed/18082611

The anaphase-promoting complex/cyclosome (APC/C) is a conserved multisubunit E3 ubiquitin (Ub) ligase required to signal the degradation of key cell-cycle regulators. Using single particle cryo-electron microscopy (cryo-EM), we have determined a three-dimensional (3D) structure of the core APC/C from Schizosaccharomyces pombe bound to the APC/C activator Slp1/Cdc20. At the 27 A resolution of our density map, the APC/C is a triangular-shaped structure, approximately 19x17x15 nm in size, with a deep internal cavity and a prominent horn-like protrusion emanating from a lip of the cavity. Using antibody labeling and mutant analysis, we have localized 12 of 13 core APC/C components, as well as the position of the activator Slp1, enabling us to propose a structural model of APC/C organization. Comparison of the APC/C with another multiprotein E3 ligase, the SCF complex, uncovers remarkable structural similarities.

Pubmed ID: 18082611 RIS Download

Mesh terms: Anaphase-Promoting Complex-Cyclosome | Cdc20 Proteins | Cell Cycle Proteins | Chromatography, Affinity | Cryoelectron Microscopy | Immunoblotting | Mitosis | Models, Molecular | Mutagenesis, Site-Directed | Mutation | Protein Conformation | Schizosaccharomyces | Schizosaccharomyces pombe Proteins | Ubiquitin-Protein Ligase Complexes | Ubiquitin-Protein Ligases | Ubiquitination

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Associated grants

  • Agency: NIBIB NIH HHS, Id: 5 P41 EB2181
  • Agency: NIGMS NIH HHS, Id: GM 60635
  • Agency: NIGMS NIH HHS, Id: GM62580
  • Agency: NIGMS NIH HHS, Id: P01 GM062580
  • Agency: NIGMS NIH HHS, Id: P01 GM062580-06A16830
  • Agency: NIGMS NIH HHS, Id: P01 GM064692

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