Toxic Activation of an AAA+ Protease by the Antibacterial Drug Cyclomarin A.

ATP-driven bacterial AAA+ proteases have been recognized as drug targets. They possess an AAA+ protein (e.g.

Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control.

Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance.