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

✍ Scribed by RAMON GONZÁLEZ; BARBARA A. ANDREWS; JUAN A. ASENJO


Publisher
Elsevier Science
Year
2002
Tongue
English
Weight
202 KB
Volume
214
Category
Article
ISSN
0022-5193

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✦ Synopsis


A mechanism for heavy chain binding protein (BiP)-and protein disul"de 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 in#uence of polypeptide concentration and ratio, and the e!ect 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 di!erent kinetic behaviors were identi"ed 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.


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