Substrate binding on the APC/C occurs between the coactivator Cdh1 and the processivity factor Doc1.
Bettina A Buschhorn1, Georg Petzold1, Marta Galova1
1Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Nature Structural & Molecular Biology
|December 28, 2010
Summary
The anaphase-promoting complex/cyclosome (APC/C) subunit Doc1 is crucial for recruiting substrates to the APC/C. This interaction, involving Doc1 and coactivator proteins, facilitates substrate ubiquitylation and subsequent mitotic exit.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The anaphase-promoting complex/cyclosome (APC/C) is a critical E3 ubiquitin ligase.
- APC/C regulates key cell cycle events, including chromosome segregation and mitotic exit.
- Understanding APC/C structure and substrate recruitment is vital for cell cycle control.
Purpose of the Study:
- To investigate the role of the APC/C subunit Doc1 in substrate recruitment and ubiquitylation.
- To elucidate the structural basis of APC/C monomer interactions and dimer formation.
- To understand how substrate binding influences APC/C conformation and activity.
Main Methods:
- Biochemical analyses of Saccharomyces cerevisiae and human APC/C.
- Electron microscopic studies of APC/C structure and interactions.
- Analysis of protein-protein interactions between APC/C subunits and substrates.
Main Results:
- Doc1 localizes within the APC/C inner cavity, near the Apc2-Apc11 module.
- Doc1 interacts with multiple APC/C core components (Cdc27, Cdc16, Apc1).
- Substrates bind in the inner cavity, close to Doc1 and Cdh1, inducing conformational changes.
Conclusions:
- Doc1 is a key component of the APC/C substrate receptor.
- Substrate recruitment involves a bipartite receptor comprising coactivator proteins and Doc1.
- These findings provide insights into the mechanism of APC/C-mediated ubiquitylation and cell cycle regulation.
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