CLPXP FUNCTIONS IN CAULOBACTER AS A UNIVERSAL AND SPECIES-SPECIFIC PROTEASE

Proteolysis shapes many aspects of cellular survival, including protein quality control and cellular signaling. Powered proteolysis couples ATP hydrolysis with a degradation force that actively probes and interrogates the protein population. ClpXP, exemplifies a conserved two-part protease system charged with powered proteolysis. This protease exists as a regulatory element (ClpX), and a compartmentalized, self-contained peptidase element (ClpP). In Caulobacter crescentus, ClpXP degradation plays a crucial role maintaining proteins that exhibit proper activity, and also triggers the start of cellular differentiation. Substrate elimination requires shared aspects of the protease from both quality control and precision protein destruction functions. Here, the regulatory element and peptidase must interact and recognize substrates for complete degradation. Discrimination between active function in quality control and protein removal used for signaling, challenges the protease to prioritize all encountered substrates. ClpXP accomplishes this task by fully exploiting ClpX N-domain specificity and a host of adaptors that effectively categorize protein degradation as quality control, cell-cycle dependent, or under replication fitness. Interestingly, ClpXP also functions to partially degrade some targeted protein substrates. One such constantly recognized protein that requires the ClpX N-domain, DnaX, undergoes partial proteolysis that generates two smaller protein forms. Multiple DnaX forms allow for clamp loading diversity, the isoforms produced in Caulobacter alternately phenocopy the activity of ribosomal slippage found in E. coli. The degratory effects that ClpXP imposes within the cell best describes the proteases’ function. Part of this process reveals some substrate recognition by a common mechanism, while a more elaborate delivery system coordinates recognition of other substrates. Further contrast of ClpX and ClpP activity between Caulobacter and Escherichia reveals that despite retaining universal purpose, these proteins evolved functions to meet the specific demands of their respective systems