Summary

Protein disulfide isomerase (E.C. 5.3.4.1) is an abundant, soluble protein found in the lumen of the endoplasmic reticulum (ER) of eukaryotic cells. It is directed accross the ER membrane at biosynthesis by a classical signal sequence and retained in the ER by a KDEL sequence on its carboxy terminus. The major role for protein disulfide isomerase is thought to be the formation and rearrangement of disulfide bonds. Protein disulfide isomerase is found in cells mainly as a homodimer.

Mechanism

Formation of a disulfide bond via the action of protein disulfide isomerase involves both oxidation and isomerization steps. The most plausible models are shown below (to be added at some point). The active site of protein disulfide isomerase resembles that of thioredoxin. Active site cysteine groups of PDI form mixed disulfides with other proteins.

Subcellular Localization

Protein disulfide isomerase is localized in the lumen of the ER at a concentration of approximately 10 mg/ml and is enriched in secretory cells.

Roles for Protein Disulfide Isomerase

Protein disulfide isomerase is a component of prolyl-4-hydroxylase (an alpha2beta2 tetramer where the beta subunits are protein disulfide isomerase), an enzyme that catalyzes the hydroxylation of prolines in procollagen during the synthesis of collagen. Protein disulfide isomerase is also a component of microsomal triacylglycerol transfer protein (a heterodimer of PDI and a 97kDa subunit), that is believed to catalyze the transfer of neutral lipid onto nascent lipoprotein particles. When complexed with either prolyl-4-hydroxylase or the microsomal triacylglycerol transfer protein, protein disulfide isomerase does not show isomerase activity suggesting that it may be acting to s abilize the complexes.

General References

Bulleid, N.J. Protein Disulfide Isomerase: Role in Biosynthesis of Secretory Proteins (1993) Advances in Protein Chemistry 44, 125-50

Noiva, R. Enzymatic Catalysis of Disulfide Formation (1994) Protein Expression and Purification 5, 1-13

Freedman, R.B., Hirst, T.R. and Tuite, M.F. Protein disulfide isomerase: building bridges in protein folding (1994) Trends in Biochemical Sciences 19, 331-336


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