Protein Disulfide Isomerase

The folding protein (and protein folder) is beset with a number of problems in translating the simple instructions encoded by DNA into the complex, three-dimensional structure of a correctly folded protein. Nature has solved these problems in an adequate, if not elegant, fashion, but we are just beginning to understand the variety of strategies that cells use to ensure efficient protein folding. This minireview will focus on several of the more general principles of assisted folding using the folding catalyst, protein disulfide isomerase (PDI), as an example. This remarkable resident of the endoplasmic reticulum (ER) inserts disulfides into folding proteins and provides a mechanism to correct errors in disulfide pairing when they occur. At high concentrations, it functions as an ATP-independent chaperone that inhibits aggregation; yet, at lower concentrations, it can also participate in an unusual interaction with substrate that leads to PDI-facilitated aggregation (anti-chaperone behavior).