Oxidative Folding of Proteins: Basic Principles, Cellular Regulation and Engineering
CHAPTER 4.4: Thioredoxin and Cellular Redox Systems: Beyond Protein Disulfide Bond Reduction
Published:27 Jul 2018
X. Ren, J. Lu, and A. Holmgren, in Oxidative Folding of Proteins: Basic Principles, Cellular Regulation and Engineering, ed. M. J. Feige, The Royal Society of Chemistry, 2018, pp. 355-378.
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Thioredoxin (Trx) and glutaredoxin (Grx) systems are the two major antioxidant systems in cells and recent studies have revealed more of their functions beyond disulfide reduction. In contrast to most cellular environments, protein oxidative folding occurs in more oxidizing compartments such as the bacterial periplasm and the eukaryotic endoplasmic reticulum. Owing to the special redox properties of Trx, the Trx superfamily proteins play essential roles in protein folding by catalyzing thiol–disulfide exchange reactions. They also facilitate protein folding by chaperone activity, coordinate iron–sulfur clusters and mediate redox signaling. Trx and Grx systems play key roles in redox signaling regulation by reactive oxygen species (ROS) scavenging, protein–protein interactions and catalyzing reversible thiol modifications, such as S-nitrosylation and glutathionylation. Transcription factors, such as bacterial OxyR or eukaryotic NFκB, and protein tyrosine kinases (PTPs) involved in receptor signaling are regulated by Trx and Grx systems.