thioredoxinlike

Thioredoxin-like refers to proteins or protein domains that resemble thioredoxin in sequence, structure, or catalytic mechanism. The canonical thioredoxin is a small, redox-active protein that uses a conserved active-site motif, typically Cys-Gly-Pro-Cys (CGPC), to catalyze thiol-disulfide exchange. Thioredoxin-like proteins share the characteristic thioredoxin fold and often rely on a redox-active disulfide to shuttle reducing equivalents.

In operation, thioredoxin-like proteins act as disulfide reductants, transferring electrons from one partner to another. They are reduced by thioredoxin reductase, using NADPH as the ultimate electron donor, and then reduce target proteins by converting their disulfide bonds to free thiols. This chemistry underpins cytosolic and organellar redox homeostasis, influences DNA synthesis via ribonucleotide reductase, and participates in redox signaling. In addition, thioredoxin-like domains are common in protein disulfide isomerases, which catalyze the formation and rearrangement of disulfide bonds during protein folding in the endoplasmic reticulum.

Diversity and distribution are broad. The term encompasses standalone thioredoxins, such as bacterial TrxA and vertebrate TXN, as well as multi-domain proteins that incorporate thioredoxin-like domains, including members of the protein disulfide isomerase family. Some thioredoxin-like domains carry altered motifs or are integrated into larger enzymes with different primary functions, yet retain redox-active cysteine residues in specific contexts.

Overall, thioredoxin-like proteins are central to cellular redox control, enabling maintenance of protein structure, redox signaling, and responses to oxidative stress across all domains of life.