Defining the mechanism of PDI interaction with disulfide-free amyloidogenic proteins: Implications for exogenous protein expression and neurodegenerative disease

Protein disulfide isomerase (PDI) is an important molecular chaperone capable of facilitating protein folding in addition to catalyzing the formation a bond. To better understand distinct substrate-screening principles Pichia pastoris PDI (Protein isomerase) and protective role amyloidogenic diseases, we investigated expression abundance intracellular retention levels three archetypal bond-free proteins (A?42, ?-synuclein (?-Syn) SAA1) P. GS115 strain without with overexpression PpPDI (P. PDI). Intriguingly, A?42 ?-Syn were detected only as whereas SAA1 was both extracellular when these expressed PpPDI-overexpressing strain. The binding between each by docking simulations. Three different patterns PpPDI-substrate complexes observed, suggesting that multiple modes might exist for its substrates, this could represent specificities affinities toward substrates. Further analysis proteomics data functional annotations indicated eliminate need misfolded be partitioned ER-associated compartments.