The protein disulphide-isomerase family: unravelling a string of folds

Abstract

The mammalian protein disulphide-isomerase (PDI) family encompasses several highly divergent proteins that are involved in the processing and maturation of secretory proteins in the endoplasmic reticulum. These proteins are characterized by the presence of one or more domains of roughly 95-110 amino acids related to the cytoplasmic protein thioredoxin. All but the PDI-D subfamily are composed entirely of repeats of such domains, with at least one domain containing and one domain lacking a redox-active -Cys-Xaa-Xaa-Cys- tetrapeptide. In addition to their known roles as redox catalysts and isomerases, the last few years have revealed additional functions of the PDI proteins, including peptide binding, cell adhesion and perhaps chaperone activities. Attention is now turning to the non-redox-active domains of the PDIs, which may play an important role in all of the known activities of these proteins. Thus the presence of both redox-active and -inactive domains within these proteins portends a complexity of functions differentially accommodated by the various family members.

Directed evolution of a three-finger neurotoxin by using cDNA display yields antagonists as well as agonists of interleukin-6 receptor signaling

“…We found that proteins refolded in the presence of reduced and oxidized glutathione (a redox pair) had random conformation, as judged from their CD spectra (Figure 4C (i)). However, when immobilized protein disulfide isomerase (PDI), a chaperone known to assist and improve folding/refolding [23], was included in the redox buffer, we observed spectra resembling β-sheets (Figure 4C (ii)). Ellipticities near 200 and 215 nm (spectra in dotted line) indicate a major β-sheet conformation [24].…”

Oxidative Stress, Unfolded Protein Response, and Apoptosis in Developmental Toxicity

“…In contrast to the reducing environment of the cytosol, the ER lumen is oxidizing, which promotes formation of disulfide bonds (Van der Vlies et al, 2003). Protein disulfide isomerase (PDI) is a member of the Prx superfamily and catalyzes disulfide bond formation, isomerization, and reduction of proteins within the ER (Ferrari and Soling, 1999). Following oxidation of protein thiols, the reduced form of PDI is oxidized by ER oxidoreductins (ERO), ERO1α, and ERO1β (Pagani et al, 2000).…”

Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery

“…PDIA4 is 645 amino acids long and has a molecular weight of 72 kDa; thus it is also known as ERP72. Most protein disulfide isomerases have three conserved domains-A, B and C. 52,53 Domain A is a catalytically active thioredoxin like domain, domain B is a catalytically inactive thioredoxin like domain and domain C is a highly acidic region which is frequently used to bind to peptides.…”