Figure 5. Working mechanism of substrate-binding of PDI.

(a) Model of closed form of fungal PDI b′–a′ domains based on the fungal PDI/αSN complex superimposed on the crystal structure of human PDI (PDB code: 3UEM). The b′ and a′ domains are shown as ribbon and surface representations, respectively, while the αSN peptide is as cyan spheres. (b) Schematic model of the redox-dependent substrate binding of PDI. PDI captures the hydrophobic segments of substrates through its hydrophobic surface (orange) exposed in the open conformation of the b′–a′ domains in its oxidized form, while reduction of the a′ active site is coupled with the interdomain b′–a′ interaction, resulting in release of the substrate with disulfide formation.