Research Spatial control of protease activity in bacteria

ATP-dependent AAA+ proteases execute general and regulatory proteolysis in bacteria and play crucial roles in stress protection and virulence. The specificities and activities of AAA+ proteases must be tightly controlled to prevent deleterious proteolysis. Here, we report on the ClpE/ClpP protease, which is a central component of bacterial protein quality control (PQC) systems. ClpE/ClpP functions autonomously and degrades various PQC substrates including aggregated proteins and the stress-responsive regulator CtsR. We show that ClpE/ClpP forms large proteolytic clusters in vitro and in E. coli cells. These clusters spatially confine proteolytic activities and preventing cluster formation creates toxicity due to uncontrolled protein degradation. Our findings suggest that control of AAA+ protease localization represents an overarching regulatory principle enhancing substrate specificity.