Protein design by fusion: implications for protein structure prediction and evolution

Acta Crystallogr D Biol Crystallogr. 2013 Dec;69(Pt 12):2451-60. doi: 10.1107/S0907444913022701. Epub 2013 Nov 19.


Domain fusion is a useful tool in protein design. Here, the structure of a fusion of the heterodimeric flagella-assembly proteins FliS and FliC is reported. Although the ability of the fusion protein to maintain the structure of the heterodimer may be apparent, threading-based structural predictions do not properly fuse the heterodimer. Additional examples of naturally occurring heterodimers that are homologous to full-length proteins were identified. These examples highlight that the designed protein was engineered by the same tools as used in the natural evolution of proteins and that heterodimeric structures contain a wealth of information, currently unused, that can improve structural predictions.

Keywords: protein design; protein fusion; protein threading; structure prediction.

MeSH terms

  • Aquifoliaceae / chemistry*
  • Aquifoliaceae / genetics
  • Crystallography, X-Ray
  • Databases, Protein
  • Evolution, Molecular
  • Models, Molecular
  • Plant Proteins / chemistry*
  • Plant Proteins / genetics
  • Protein Conformation
  • Protein Engineering
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Structural Homology, Protein


  • Plant Proteins
  • Recombinant Fusion Proteins

Associated data

  • PDB/4IWB