Chapter 31

HtrA proteases are dual-function chaperone-protease protein quality control systems. The protease activity of HtrA proteases depends on a proper spatial relationship between the Asp-His-Ser catalytic triad. Propose a mechanism for the temperature-induced switch of HtrA proteases from chaperone function to protease function.

As described in this chapter, the most common post-translational modifications of proteins are proteolysis, phosphorylation, methylation, acetylation, and linkage with ubiquitin and SUMO proteins. Carry out a Web search to identify at least eight other post translational modifications and the amino acid residues involved in these modifications.

Fluorescence resonance energy transfer (FRET) is a spectroscopic technique that can be used to provide certain details of the conformation of biomolecules. Look up FRET on the Web or in an introductory text on FRET uses in biochemistry, and explain how FRET could be used to observe conformational changes in proteins bound to chaperonins such as GroEL. A good article on FRET in protein folding and dynamics can be found here: Haas, E., 2005. The study of protein folding and dynamics by determination of intramolecular distance distributions and their fluctuations using ensemble and single-molecule FRET measurements. ChemPhysChem \(6: 858-870 .\) Studies of GroEL using FRET analysis include the following: Sharma, S., et al., 2008. Monitoring protein conformation along the pathway of chaperonin-assisted folding. Cell \(133: 142-153\); and \(\mathrm{Lin}, \mathrm{Z},\) et al. \(, 2008 .\) GroEL stimulates protein folding through forced unfolding. Nature Structural and Molecular Biology \(15: 303-311\)

The cross-talk between phosphorylation and ubiquitination in protein degradation processes is encapsulated in the concept of the "phosphodegron." What is a phosphodegron, and how does phosphorylation serve as a recognition signal for protein degradation? (A good reference on the phosphodegron and crosstalk between phosphorylation and ubiquitination is Hunter, \(\mathrm{T}\)., 2007 . The age of crosstalk: Phosphorylation, ubiquitination, and beyond. Molecular Cell \(28: 730-738 .\)

A common post-translational modification is removal of the universal N-terminal methionine in many proteins by Met-aminopeptidase. How might Met removal affect the half-life of the protein?