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Examining Proteasome Assembly with Recombinant Archaeal Proteasomes and Nondenaturing PAGE: The Case for a Combined Approach
Published on: December 17, 2016
Structural basis for the subunit assembly of the anaphase-promoting complex
Anne Schreiber1, Florian Stengel, Ziguo Zhang
1Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.
Nature
|February 11, 2011
Summary
The anaphase-promoting complex (APC/C), a large E3 ubiquitin ligase, has its structure revealed. This study defines the organization and interactions of its subunits, providing a pseudo-atomic model for 70% of the complex.
Area of Science:
- Cell Biology
- Structural Biology
- Biochemistry
Background:
- The anaphase-promoting complex or cyclosome (APC/C) is a crucial E3 ubiquitin ligase regulating cell cycle transitions.
- Detailed understanding of APC/C assembly and subunit interactions remains limited.
Purpose of the Study:
- To reconstitute holo APC/C and its sub-complexes using a recombinant expression system.
- To determine the precise organization and structure of APC/C subunits and their interactions.
Main Methods:
- Recombinant expression and reconstitution of APC/C and sub-complexes.
- Cryo-electron microscopy and mass spectrometry.
- Docking of crystallographic and homology-derived coordinates.
Main Results:
- A pseudo-atomic model was generated for 70% of the APC/C, revealing its lattice-like structure.
- Three conserved tetratricopeptide repeat (TPR) subunits (Cdc16, Cdc23, Cdc27) form a quasi-symmetrical structure.
- Scaffolding subunits coordinate the catalytic module, substrate recognition module, and regulatory sites.
Conclusions:
- The study provides unprecedented structural insights into the APC/C complex.
- The defined structure elucidates how APC/C subunits assemble and interact with regulatory factors.
- This work lays the foundation for understanding APC/C function in cell cycle regulation.
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