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Structural basis for the regulated protease and chaperone function of DegP
Tobias Krojer1, Justyna Sawa, Eva Schäfer
1Research Institute for Molecular Pathology - IMP, Dr Bohrgasse 7, A-1030 Vienna, Austria.
Nature
|May 23, 2008
Summary
The bacterial heat-shock protein DegP acts as a quality control factor, eliminating misfolded proteins and aiding in outer-membrane protein biogenesis. Misfolded proteins trigger DegP to form larger, active complexes that package or degrade substrates.
Area of Science:
- Bacterial protein quality control
- Molecular mechanisms of protein folding
- Heat shock proteins and cellular stress response
Background:
- Organisms require precise monitoring of cellular protein folding states.
- DegP (DegP) is a crucial heat-shock protein in the bacterial envelope.
- DegP functions in eliminating misfolded proteins and biogenesis of outer-membrane proteins.
Purpose of the Study:
- To elucidate the molecular mechanisms behind the regulated protease and chaperone functions of Escherichia coli DegP.
- To understand how DegP transitions between different oligomeric states and activities.
Main Methods:
- Structural analysis of DegP multimers.
- Investigating the role of substrate binding in DegP activation.
- Biochemical assays to characterize protease and chaperone activities.
Main Results:
- Misfolded protein binding induces hexameric DegP to form catalytically active 12-meric and 24-meric multimers.
- DegP functions as a protein packaging device with an adaptable central compartment.
- The DegP inner cavity performs dual roles: protection of folded proteins and degradation of misfolded proteins.
Conclusions:
- Substrate-induced oligomerization and activation of DegP are key to its function.
- DegP's adaptable structure facilitates its roles in protein quality control.
- Similar mechanisms may regulate other HtrA proteases involved in protein-folding diseases.
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