Incorporating electron-transfer functionality into synthetic metalloproteins from the bottom-up

Inorg Chem. 2006 Dec 11;45(25):9974-84. doi: 10.1021/ic060222j.

Abstract

The alpha-helical coiled-coil motif serves as a robust scaffold for incorporating electron-transfer (ET) functionality into synthetic metalloproteins. These structures consist of a supercoiling of two or more aplha helices that are formed by the self-assembly of individual polypeptide chains whose sequences contain a repeating pattern of hydrophobic and hydrophilic residues. Early work from our group attached abiotic Ru-based redox sites to the most surface-exposed positions of two stranded coiled-coils and used electron-pulse radiolysis to study both intra- and intermolecular ET reactions in these systems. Later work used smaller metallopeptides to investigate the effects of conformational gating within electrostatic peptide-protein complexes. We have recently designed the C16C19-GGY peptide, which contains Cys residues located at both the "a" and "d" positions of its third heptad repeat in order to construct a nativelike metal-binding domain within its hydrophobic core. It was shown that the binding of both Cd(II) and Cu(I) ions induces the peptide to undergo a conformational change from a disordered random coil to a metal-bridged coiled-coil. However, whereas the Cd(II)-protein exists as a two-stranded coiled-coil, the Cu(I) derivative exists as a four-stranded coiled-coil. Upon the incorporation of other metal ions, metal-bridged peptide dimers, tetramers, and hexamers are formed. The Cu(I)-protein is of particular interest because it exhibits a long-lived (microsecond) room-temperature luminescence at 600 nm. The luminophore in this protein is thought to be a multinuclear CuI4Cys4(N/O)4 cage complex, which can be quenched by exogenous electron acceptors in solution, as shown by emission-lifetime and transient-absorption experiments. It is anticipated that further investigation into these systems will contribute to the expanding effort of bioinorganic chemists to prepare new kinds of functionally active synthetic metalloproteins.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cadmium / chemistry
  • Computer Simulation
  • Copper / chemistry
  • Cysteine / chemistry
  • Cysteine / metabolism
  • Dimerization
  • Electron Transport / physiology*
  • Hydrophobic and Hydrophilic Interactions
  • Metalloproteins / chemistry*
  • Metalloproteins / metabolism
  • Metals / chemistry*
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Peptides / chemistry*
  • Peptides / metabolism
  • Protein Structure, Secondary
  • Ruthenium / chemistry
  • Static Electricity
  • Time Factors
  • Viscosity

Substances

  • Metalloproteins
  • Metals
  • Peptides
  • Cadmium
  • Copper
  • Ruthenium
  • Cysteine