Abstract
PROTEIN disulphide isomerase (PDI)1,2 is a highly abundant and ubiquitous eukaryotic protein that is essential for viability in yeast3,4. Although PDI is thought to catalyse disulphide bond formation and isomerization during protein biosynthesis, PDI has been found previously to have only moderate effects (∼25-fold) on the rate of oxidative folding of proteins in vitro. In addition, PDI has been implicated in several apparently unrelated cellular functions3. For example, PDI is the β-subunit of prolyl 4-hydroxylase5 and is part of the trigylceride transfer complex6. The oxidative folding of bovine pancreatic trypsin inhibitor (BPTI) is slow and inefficient in vitro7–11. 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.
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Weissman, J., Kimt, P. Efficient catalysis of disulphide bond rearrangements by protein disulphide isomerase. Nature 365, 185–188 (1993). https://doi.org/10.1038/365185a0
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DOI: https://doi.org/10.1038/365185a0
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