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Structure of the anaphase-promoting complex/cyclosome interacting with a mitotic checkpoint complex
Franz Herzog1, Ivana Primorac, Prakash Dube
1Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
The mitotic checkpoint complex (MCC) inhibits the anaphase-promoting complex/cyclosome (APC/C) by binding to its Cdc20 coactivator. This structural study reveals how MCC locks APC/C in a closed state, preventing anaphase onset.
Area of Science:
- Cell Biology
- Molecular Biology
- Structural Biology
Background:
- Anaphase onset requires the anaphase-promoting complex/cyclosome (APC/C) and its coactivator Cdc20.
- The mitotic checkpoint complex (MCC) prevents premature anaphase by inhibiting APC/C(Cdc20).
Purpose of the Study:
- To elucidate the structural mechanism by which MCC inhibits APC/C(Cdc20).
Main Methods:
- Single-particle electron microscopy was used to generate 3D models of human APC/C in different functional states.
Main Results:
- MCC binds to the Cdc20 binding site on APC/C.
- MCC locks APC/C in a closed conformation, preventing substrate binding and ubiquitylation.
- Structural models were obtained for apo-APC/C, APC/C-MCC, and APC/C-Cdc20.
Conclusions:
- The study clarifies the structural basis for MCC-mediated inhibition of APC/C.
- Understanding this mechanism is crucial for comprehending cell cycle regulation and mitotic fidelity.
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