The study delves into the intricate workings of the DegP protease-chaperone, a crucial component in the protein homeostasis of Gram-negative bacteria. It focuses on understanding how DegP cages encapsulate and interact with client proteins, particularly through the lens of a model α-helical client protein. The research employs hydrodynamics measurements, solution nuclear magnetic resonance studies, and proteolytic activity assays to explore these interactions throughout the DegP activation cycle. Key findings reveal that DegP cages assemble cooperatively with minimal intermediates when a client is present. The client’s N-terminal half within the cage is largely unfolded, flexible, and transitions between multiple conformational states. Importantly, the engagement of a client triggers a structural transition in DegP’s protease domains, activating the system. This study highlights DegP’s role as a dynamic molecular machine that stabilizes unfolded client proteins, facilitating efficient cleavage. This contributes significantly to our understanding of protein homeostasis mechanisms in bacteria, with potential implications for targeting bacterial virulence and stress response pathways.