Abstract
For proteins that are processed in the eukaryotic endoplasmic reticulum and destined for the cell surface, the correct formation of protein disulfides is critical to their folding and function. Protein disulfide isomerase (PDI) is a resident of the endoplasmic reticulum that catalyzes disulfide formation and also provides mechanisms to correct folding mistakes. The protein consists of multiple thioredoxin domains with one or more active sites, generally in the sequence CGHC. The active site cycles between an oxidized (disulfide) state which can catalyze disulfide formation and a reduced (dithiol) state that can break disulfides that are incorrectly paired. During the folding of disulfide-containing proteins, the folding process must allow the proper cysteines to closely approach each other while allowing steric access to oxidants. Early in folding, disulfide formation is error-prone and a mechanism is required to break incorrect disulfides. In addition to catalyzing disulfide formation, PDI provides this critical proof-reading function as well. In this chapter, we consider the structural organization of PDIs, their chemical and catalytic properties, the factors that may affect specificity, and their role in the eukaryotic cell.
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Gilbert, H.F. (2011). Protein Disulfide Isomerase and the Catalysis of Oxidative Protein Folding. In: Chang, R., Ventura, S. (eds) Folding of Disulfide Proteins. Protein Reviews, vol 14. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7273-6_7
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