Genome-wide analysis of eukaryotic twin CX9C proteins

Mol Biosyst. 2010 Dec;6(12):2459-70. doi: 10.1039/c0mb00058b. Epub 2010 Oct 4.


Twin CX(9)C proteins are eukaryotic proteins that derive their name from their characteristic motif, consisting of two pairs of cysteines that form two disulfide bonds stabilizing a coiled coil-helix-coiled coil-helix (CHCH) fold. The best characterized of these proteins are Cox17, a copper chaperone acting in cytochrome c oxidase biogenesis, and Mia40, the central component of a system for protein import into the mitochondrial inter-membrane space (IMS). However, the range of possible functions for these proteins is unclear. Here, we performed a systematic search of twin CX(9)C proteins in eukaryotic organisms, and classified them into groups of putative homologues, by combining bioinformatics methods with literature analysis. Our results suggest that the functions of most twin CX(9)C proteins vary around the common theme of playing a scaffolding role, which can tie their observed roles in mitochondrial structure and function. This study will enhance the present annotation of eukaryotic proteomes, and will provide a rational basis for future experimental work aimed at a deeper understanding of this remarkable class of proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acids
  • Animals
  • Cluster Analysis
  • Eukaryotic Cells / metabolism*
  • Genome / genetics*
  • Humans
  • Mitochondria / metabolism
  • Mitochondrial Proteins / chemistry*
  • Mitochondrial Proteins / metabolism*
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Phylogeny
  • Protein Structure, Secondary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Saccharomyces cerevisiae / metabolism


  • Amino Acids
  • Mitochondrial Proteins
  • Multiprotein Complexes
  • Protein Subunits