Crystal structure of an unusual thioredoxin protein with a zinc finger domain.

Many Gram-negative bacteria have two cytoplasmic thioredoxins, thioredoxin-1 and -2, encoded by the trxA and trxC genes, respectively. Both thioredoxins have the highly conserved WCGPC motif and function as disulfide-bond reductases. However, thioredoxin-2 has unique features: it has an N-terminal motif that binds a zinc ion, and its transcription is under the control of OxyR, which allows it to be up-regulated under oxidative stress. Here, we report the crystal structure of thioredoxin-2 from Rhodobacter capsulatus. The C-terminal region of thioredoxin-2 forms a canonical thioredoxin fold with a central beta-sheet consisting of five strands and four flanking alpha-helices on either side. The N-terminal zinc finger is composed of four short beta-strands (S1-S4) connected by three short loops (L1-L3). The four cysteines are at loops L1 and L3 and form a tetragonal binding site for a zinc ion. The zinc finger is close to the first beta-strand and first alpha-helix of the thioredoxin fold. Nevertheless, the zinc finger may not directly affect the oxidoreductase activity of thioredoxin-2 because the zinc finger is not near the active site of a protomer and because thioredoxin-2 is a monomer in solution. On the basis of structural similarity to the zinc fingers in Npl4 and Vps36, we propose that the N-terminal zinc finger of thioredoxin-2 mediates protein-protein interactions, possibly with its substrates or chaperones.