A comprehensive approach to identify redox and non-redox targets of Trx-like proteins

by Lia S. Nakao

Like the old dictum that says “birds of a feather flock together”, understanding the specific partners of a given protein provides an important clue about its function. Thioredoxin 1 (Trx1) is a well-known redox protein that contains a CXXC motif (cysteines residues flanking two aminoacid residues), responsible for its disulfide reductase function. The first (C-terminal) Cys of the motif attacks the disulfide of the target protein, producing a short lived mixed disulfide, which is reduced by the second (N-terminal resolving) Cys, releasing Trx1 and the target, in the oxidized and reduced forms, respectively. If the resolving Cys is replaced by a non-redox residue, such as