Protein degradation in bacteria is a highly controlled process involving proteolytic adaptors that regulate protein degradation during cell cycle progression or during stress responses. Many adaptors work as scaffolds that selectively bind cargo and tether substrates to their cognate proteases to promote substrate destruction, whereas others primarily activate the target protease. Because adaptors must bind their cognate protease, all adaptors run the risk of being recognized by the protease as substrates themselves, a process that could limit their effectiveness. Here we use purified proteins in a reconstituted system and in vivo studies to show that adaptors of the ClpXP protease are readily degraded but that cargo binding inhibits this degradation. We found that this principle extends across several adaptor systems, including the hierarchical adaptors that drive the Caulobacter bacterial cell cycle and the quality control adaptor SspB. We also found that the ability of a cargo to protect its adaptor is adaptor substrate-specific, as adaptors with artificial degradation tags were not protected even though cargo binding is unaffected. Our work points to an optimization of inherent adaptor degradation and cargo binding that ensures that robust adaptor activity is maintained when high amounts of substrate must be delivered and that adaptors can be eliminated when their tasks have been completed.
Keywords: ATP-dependent protease; ATPases associated with diverse cellular activities (AAA); Caulobacter; ClpXP; RcdA; SspB; adaptor protein; bacteria; cell cycle.
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.