Synergistic effect is mediated by the a′ domain of PDI. (A) Schematic model of electron transfer relays between Ero1-α and PDI. Ero1-α oxidizes the a′ domain of PDI, which in turn oxidizes the a domain internally. The oxidized a domain is rereduced by GSH. (B) Kinetics of oxygen consumption by 2 µM constitutively active Ero1-α(C104A/C131A) during the reaction with 5 µM human PDI variants, as depicted in the figure, in the presence of 10 mM GSH. (C–G) Oxygen consumption was assayed in the presence of 10 mM GSH and 10 µM ERp46 (C) with or without 5 µM PDI(a) or 10 µM ERp46 (D), ERp57 (E), P5 (F), or ERp72 (G) with or without 5 µM PDI(a′). Calc shows the calculation data from individual consumption rates of these oxidoreductases. Mix represents the actual consumption rates under conditions in which 10 µM of each oxidoreductase and 5 µM PDI were mixed in the presence of 10 mM GSH. (H) Schematic model of electron transfer relays among Ero1-α, the a′ domain of PDI, and oxidoreductases (ERp46, ERp57, and P5). ROS, reactive oxygen species.