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Insights into anaphase promoting complex TPR subdomain assembly from a CDC26-APC6 structure
Jing Wang1, Billy T Dye, Kanagalaghatta R Rajashankar
1Departments of Structural Biology and Genetics/Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Nature Structural & Molecular Biology
|August 12, 2009
Summary
CDC26 stabilizes the anaphase promoting complex (APC) by interacting with APC6, a core protein. This interaction, involving a TPR mimic, is crucial for maintaining APC integrity and cell-cycle regulation.
Area of Science:
- Cell Biology
- Molecular Biology
- Structural Biology
Background:
- The anaphase promoting complex (APC) is a critical regulator of the cell cycle.
- The precise molecular function of CDC26 in APC assembly has been previously undetermined.
Purpose of the Study:
- To elucidate the molecular function of CDC26 in the context of APC assembly and integrity.
- To determine the structural basis of CDC26-APC6 interaction.
Main Methods:
- Biophysical techniques
- Structural biology methods
- Genetic studies
Main Results:
- CDC26 stabilizes the structure of APC6, a core tetratricopeptide repeat (TPR) protein essential for APC integrity.
- The association between CDC26 and APC6 involves an intermolecular TPR mimic, with a helix from each protein contributing to the interaction.
- This stabilization is critical for the overall integrity of the multisubunit APC.
Conclusions:
- CDC26 plays a vital role in maintaining APC integrity through direct stabilization of APC6.
- The identified intermolecular TPR mimic mechanism provides new insights into protein-protein interactions within the APC.
- Understanding CDC26 function is key to comprehending cell-cycle regulation and potential therapeutic targets.
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