The fold is named for the canonical example thioredoxin and is found in both prokaryotic and eukaryotic proteins.

The fold's spatial topology consists of a four-stranded antiparallel beta sheet sandwiched between three alpha helices.

Despite sequence variability in many regions of the fold, thioredoxin proteins share a common active site sequence with two reactive cysteine residues: Cys-X-Y-Cys, where X and Y are often but not necessarily hydrophobic amino acids.

Different thioredoxin fold-containing proteins vary greatly in their reactivity and in the pKa of their free thiols, which derives from the ability of the overall protein structure to stabilize the activated thiolate.

Although the structure is fairly consistent among proteins containing the thioredoxin fold, the pKa is extremely sensitive to small variations in structure, especially in the placement of protein backbone atoms near the first cysteine.