Model of inter- and intramolecular electron transfer cascade between ERO1 and PDI in humans. In the oxidation of PDI by ERO1, ERO1 transfers electrons from the active center of PDI domain a′ to O2. In PDI, electrons are transferred intramolecularly from domain a to domain a′. The black ellipses indicate the reduced domains a or a′ of PDI, and the red ellipses indicate the oxidized domains. The gray ellipses indicate PDI domain b or b′. For ERO1, the two SH and S–S (black text) indicate the thiols and disulfide of the shuttle cysteine pair, and the S–S (green text) indicates the disulfide of the active cysteine pair. In inactive form (ox-2) of ERO1, the regulatory cysteines (red) formed disulfide bonds with the shuttle cysteines, which are reduced in active form (ox-1).