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.
Ye
Jiqing
J
Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cho
Seung-Hyun
SH
Fuselier
Jessica
J
Li
Weikai
W
Beckwith
Jon
J
Rapoport
Tom A
TA
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007477:Ions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016354:Rhodobacter capsulatus / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry; D016335:Zinc Fingers
D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D007477:Ions; D013879:Thioredoxins; C063842:dnaK protein, E coli; D015032:Zinc