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

J Biol Chem. 2007 Nov 30;282(48):34945-51. doi: 10.1074/jbc.M704044200. Epub 2007 Oct 3.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Escherichia coli Proteins / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • Ions
  • Models, Molecular
  • Molecular Sequence Data
  • Oxidative Stress
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Rhodobacter capsulatus / metabolism
  • Sequence Homology, Amino Acid
  • Thioredoxins / chemistry*
  • Zinc / chemistry
  • Zinc Fingers

Substances

  • Escherichia coli Proteins
  • HSP70 Heat-Shock Proteins
  • Ions
  • Thioredoxins
  • dnaK protein, E coli
  • Zinc

Associated data

  • PDB/2PPT