Peptidyl-prolyl cis-trans isomerase improves the efficiency of protein disulfide isomerase as a catalyst of protein folding.
The cis-trans isomerization of prolyl peptide bonds and the formation of disulfide bonds are both slow steps in protein folding. By using ribonuclease T1 as a model system, we show that these two processes can become linked in the oxidative folding of reduced proteins and that the formation of the correct disulfide bonds is facilitated in the presence of peptidyl-prolyl cis-trans isomerase. In particular, the efficiency of protein disulfide isomerase (EC 5.3.4.1) as a catalyst of disulfide bond formation in the course of oxidative folding is markedly improved when peptidyl-prolyl cis-trans isomerase is present simultaneously. Possibly, unfolded or partially folded protein chains with correct prolyl isomers are better substrates for catalysis by protein disulfide isomerase. The interdependence of the two enzymatic activities detected during in vitro folding experiments could be of importance for the de novo folding and disulfide bond formation of nascent proteins in the endoplasmic reticulum.
Schönbrunner
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Biochemisches Laboratorium, Universität Bayreuth, Federal Republic of Germany.
Schmid
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D000591:Amino Acid Isomerases / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D007535:Isomerases / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D010084:Oxidation-Reduction; D019696:Peptidylprolyl Isomerase; D011487:Protein Conformation; D011489:Protein Denaturation; D019704:Protein Disulfide-Isomerases; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D006163:Ribonuclease T1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D002352:Carrier Proteins; D011994:Recombinant Proteins; D006163:Ribonuclease T1; D007535:Isomerases; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; D019704:Protein Disulfide-Isomerases