Oxidative protein folding is driven by the electron transport system

Disulfide bond formation is catalyzed in vivo by DsbA and DsbB. Here we rec onstitute this oxidative folding system using purified components. We have found the sources of oxidative power for protein folding and show how disul fide bond formation is linked to cellular metabolism. We find that disulfid e bond formation and the electron transport chain are directly coupled. Dsb B uses quinones as electron accepters, allowing various choices for electro n transport to support disulfide bond formation. Electrons flow via cytochr ome bo oxidase to oxygen under aerobic conditions or via cytochrome bd oxid ase under partially anaerobic conditions. Under truly anaerobic conditions, menaquinone shuttles electrons to alternate final electron accepters such as fumarate. This flexibility reflects the vital nature of the disulfide ca talytic system.