title: Efficient catalysis of disulphide bond rearrangements by protein disulphide isomerase.
abstract: Protein disulphide isomerase (PDI) is a highly abundant and ubiquitous eukaryotic protein that is essential for viability in yeast. Although PDI is thought to catalyse disulphide bond formation and isomerization during protein biosynthesis, PDI has been found previously to have only moderate effects (approximately 25-fold) on the rate of oxidative folding of proteins in vitro. In addition, PDI has been implicated in several apparently unrelated cellular functions. For example, PDI is the beta-subunit of prolyl 4-hydroxylase and is part of the triglyceride transfer complex. The oxidative folding of bovine pancreatic trypsin inhibitor (BPTI) is slow and inefficient in vitro. Here we report that PDI increases by a factor of 3,000-6,000 the rates of folding of kinetically trapped BPTI folding intermediates, in which native structure impedes disulphide bond formation. By contrast, PDI has only small effects on the rate of disulphide bond formation in intermediates that are oxidized readily in the absence of PDI. These results suggest that an important function of PDI is to catalyse disulphide bond formation and rearrangements within kinetically trapped, structured folding intermediates.
authors.affiliation: Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Physics, Cambridge, Massachusetts 02142.
authors.forename: J S
authors.initials: JS
authors.lastname: Weissman
authors.forename: P S
authors.initials: PS
authors.lastname: Kim
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D002417:Cattle; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism*; D007535:Isomerases / Q000378:metabolism*; D010084:Oxidation-Reduction; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases; D017510:Protein Folding
chemical_list: D004220:Disulfides; D007611:Aprotinin; D007535:Isomerases; D019704:Protein Disulfide-Isomerases