Exploring hidden features of the GroEL/ES system : how it uses a molecular device for the redox quality control of its substrates

The GroEL/ES system belongs to an essential class of chaperones found in all life forms. It uses ATP-regulated cycles to prevent unproductive interactions within and between polypeptides. Recent research has shown that CnoX, a holdase protein with a redox-protective function, directly transfers its substrates to the GroEL/ES system, a groundbreaking discovery. The goal of this thesis was to investigate the molecular interplay between CnoX and GroEL/ES and to understand their cooperation at the molecular level. We first showed that CnoX and GroEL form a stable complex even in the absence of stress and that GroES triggers the release of CnoX from GroEL. This interaction between CnoX and GroEL is facilitated by the last C-terminal α-helix of CnoX, which binds to GroEL near the substrate entry site. In addition, we showed that CnoX forms mixed disulfides with GroEL substrates when bound to GroEL in the cell, providing them with redox quality control.