Regulatory Subunits of Energy-Dependent Proteases

Abstract

The regulatory components of the energy-dependent proteases provide controlled access to the proteolytic components, which innately possess broad specificity of peptide bond cleavage. The existence of multiple regulatory complexes capable of interacting with the same proteolytic component (e.g., ClpAP and ClpXP) provides a means of further regulation by increasing the range of substrate specificity of the protease without losing selectivity. Such a combinatorial approach to assembling different types of regulatory complexes may be used to direct degradative activity toward specific proteins or classes of proteins in different cell types or in response to regulatory signals. Once a substrate is recognized, ATP-dependent unfolding and translocation moves it into the proteolytic cavity. Interactions with additional factors can further modify both substrate selection and the specificity of peptide bond cleavage to control not only the proteins targeted but also the peptide output from proteolysis. By controlling these instruments of protein destruction, the cell has added enormously to its ability to regulate the levels and activities of important regulatory proteins.‡To whom correspondence should be addressed.