Chaperone properties of Escherichia coli thioredoxin and thioredoxin reductase

Abstract

Thioredoxin, thioredoxin reductase and NADPH form the thioredoxin system and are the major cellular protein disulphide reductase. We report here that Escherichia coli thioredoxin and thioredoxin reductase interact with unfolded and denatured proteins, in a manner similar to that of molecular chaperones that are involved in protein folding and protein renaturation after stress. Thioredoxin and/or thioredoxin reductase promote the functional folding of citrate synthase and alpha-glucosidase after urea denaturation. They also promote the functional folding of the bacterial galactose receptor, a protein without any cysteines. Furthermore, redox cycling of thioredoxin/thioredoxin reductase in the presence of NADPH and cystine stimulates the renaturation of the galactose receptor, suggesting that the thioredoxin system functions like a redox-powered chaperone machine. Thioredoxin reductase prevents the aggregation of citrate synthase under heat-shock conditions. It forms complexes that are more stable than those formed by thioredoxin with several unfolded proteins such as reduced carboxymethyl alpha-lactalbumin and unfolded bovine pancreatic trypsin inhibitor. These results suggest that the thioredoxin system, in addition to its protein disulphide isomerase activity possesses chaperone-like properties, and that its thioredoxin reductase component plays a major role in this function.

Two Thioredoxin Reductases, trxr-1 and trxr-2, Have Differential Physiological Roles in Caenorhabditis elegans

“…Mitochondria may play a dominant role in aging process and development in worms, and mitochondrial TrxR may contribute to protect mitochondria from the oxidative damage. In those regards, it has been shown that the deficiency of mitochondrial redox enzymes results in the increased sensitivity to the oxidative stress and mitochondrial defects in C. elegans (Kern et al, 2003). Interestingly, the depletion of trxr-2, but not trx-2 has been reported to aggravate aging-dependent paralysis caused by the muscle-specific expression of human β-amyloid, which forms pathological plaque aggregates in the brain of Alzheimer's disease patients where the oxidative stress is a prominent factor of the disease etiology (Barstead, 1999a).…”

Proteomic analysis of thioredoxin-targeted proteins in Escherichia coli

“…Immature conformers of OmpA fold in the periplasm (43). Thioredoxin has a chaperone activity (44), and the colocalization of thioredoxin could be indicative of a role in protein folding in the periplasm. This association may also indicate a role for thioredoxin as a receptor for bacteriophages.…”

Heat-shock dependent oligomeric status alters the function of a plant-specific thioredoxin-like protein, AtTDX

“…Given that the E. coli Trx (19) and PDI (20), which contain a Trx motif and 2 Cys Prxs (14) with a Trx fold, exhibit chaperone functions, we explored the functions of AtTDX from Arabidopsis in the present study. We demonstrated in a plant system that an Arabidopsis Trx-like protein, AtTDX, displayed multiple functions that depended on its oligomeric status, alternatively acting as a disulfide reductase, foldase chaperone, and holdase chaperone.…”

“…1D). In addition, given that E. coli Trx exhibits a foldase chaperone function (19), we also examined the foldase chaperone activity of AtTDX by using glucose-6-phosphate dehydrogenase (G6PDH). To distinguish the foldase chaperone function of AtTDX from its disulfide reductase function, the Cys-free form of G6PDH was used (21).…”