Structural determinants of regulated proteolysis in pathogenic bacteria by ClpP and the proteasome

Bacteria use gated proteolytic machines for routine protein quality control and regulated responses to environmental conditions. This review discusses recent advances in understanding the structure and regulation of ClpP proteases, nanomachines widely distributed across bacteria, and the bacterial proteasome, a protease found in relatively few species. For both machines, activators confer substrate specificity. We highlight new data from organisms encoding two ClpP isoforms and the central role of activators as platforms for integrating regulatory signals. Because proteolytic systems contribute to survival and virulence of many bacterial pathogens, understanding their forms and functions enables new approaches to design targeted therapeutics.