Kinetic Model of BiP- and PDI-mediated Protein Folding and Assembly

A mechanism for heavy chain binding protein (BiP)- and protein disulfide isomerase (PDI)- mediated protein folding and assembly has been proposed. It considers BiP chaperoning action and PDI catalytic activity. A kinetic model has been developed based on the proposed mechanism. The model was used for quantifying the influence of polypeptide concentration and ratio, and the effect of BiP and PDI concentration on the kinetics of folding and assembly. An optimum value for polypeptide concentration that minimizes assembly times was found, and different kinetic behaviors were identified for polypeptide concentrations higher or lower than the optimum. Pulse-chase experiments and the dependence of assembly time on unassembled polypeptides ratio predicted by the model are similar to those found during in vitro and in vivo folding and assembly of antibodies and human chorionic gonadotropin (hCG), as well as bovine pancreatic trypsin inhibitor (BPTI) folding. The model also explains the increase in folding and assembly rates during overexpression of BiP and PDI.