Rational design of a mononuclear metal site into the archaeal Rieske-type protein scaffold

J Biol Chem. 2005 Mar 11;280(10):9129-34. doi: 10.1074/jbc.M414051200. Epub 2005 Jan 4.

Abstract

Proteins containing Rieske-type [2Fe-2S] clusters play essential functions in all three domains of life. We engineered the two histidine ligands to the Rieske-type [2Fe-2S] cluster in the hyperthermophilic archaeal Rieske-type ferredoxin from Sulfolobus solfataricus to modify types and spacing of ligands and successfully converted the metal and cluster type at the redox-active site with a minimal structural change to a native Rieske-type protein scaffold. Spectroscopic analyses unambiguously established a rubredoxin-type mononuclear Fe3+/2+ center at the engineered local metal-binding site (Zn2+ occupies the iron site depending on the expression conditions). These results show the importance of types and spacing of ligands in the in vivo cluster recognition/insertion/assembly in biological metallosulfur protein scaffolds. We suggest that early ligand substitution and displacement events at the local metal-binding site(s) might have primarily allowed the metal and cluster type conversion in ancestral redox protein modules, which greatly enhanced their capabilities of conducting a wide range of unique redox chemistry in biological electron transfer conduits, using a limited number of basic protein scaffolds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Archaeal Proteins / chemistry
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism*
  • Binding Sites
  • Cattle
  • Electron Transport Complex III / chemistry
  • Electron Transport Complex III / metabolism*
  • Ferredoxins / metabolism*
  • Iron / metabolism
  • Iron-Sulfur Proteins / chemistry
  • Iron-Sulfur Proteins / metabolism*
  • Ligands
  • Metals / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Open Reading Frames
  • Oxidation-Reduction
  • Protein Conformation
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sulfolobus / metabolism*
  • Zinc / metabolism

Substances

  • Archaeal Proteins
  • Ferredoxins
  • Iron-Sulfur Proteins
  • Ligands
  • Metals
  • Rieske iron-sulfur protein
  • Iron
  • Electron Transport Complex III
  • Zinc