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Updated: Jun 19, 2026
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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 models for interactions between the 20S proteasome and its PAN/19S activators
Beth M Stadtmueller1, Katherine Ferrell, Frank G Whitby
1Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
The Journal of Biological Chemistry
|November 6, 2009
Summary
Proteasome activators like PA26 and PAN/19S bind to proteasome gate pockets. Both use C-terminal residues to directly open the gate by contacting the Pro-17 reverse turn, revealing a conserved mechanism.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Proteasome activity is regulated by a barrel-shaped structure limiting substrate access.
- Activator complexes facilitate substrate entry by opening the proteasome's axial pore.
- PA26 and PAN/19S are distinct activator complexes with different proposed gate-opening mechanisms.
Purpose of the Study:
- To investigate the binding and gate-opening mechanisms of PA26 and PAN/19S proteasome activators.
- To compare the structural basis of gate opening induced by PA26 and PAN/19S.
Main Methods:
- X-ray crystallography to determine structures of proteasome complexes.
- Binding studies using modified PA26 constructs, including those mimicking PAN.
Main Results:
- PA26 and PAN/19S C-terminal residues bind to superimposable pockets on the proteasome.
- Both activator classes induce gate opening via direct contact with the proteasome Pro-17 reverse turn.
- A penultimate tyrosine/phenylalanine residue in PAN/19S stabilizes the open conformation through interaction with Gly-19.
Conclusions:
- PA26 and PAN/19S employ a conserved mechanism for proteasome gate opening.
- Direct contact with the Pro-17 reverse turn is crucial for activator-induced gate opening.
- Structural insights clarify how different activators regulate proteasome substrate entry.
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