Bacterial AAA+ Protease: Activity Control and Toxic Deregulation

This lecture explores the activity control and toxic deregulation of a bacterial AAA+ protease, focusing on the role of AAA+ machines in protein quality control, the modular architecture of AAA+ proteins, and the global activity control of the ClpC/ClpP protease by the adapter protein MecA. The cryo EM structures of the S. aureus MecA/ClpC/ClpP complex and the ClpC-ATPYS complex are discussed, along with the diverse activity states in the ClpC AAA2 ring. The lecture also delves into the mechanisms of ClpC activity control, the structural elements mediating ClpC/ClpP complex formation, and the potential of drug-induced activation of ClpC to create toxicity.