Structural assessment of the tetramerization domain and DNA-binding domain of CP2c

Abstract

Although the transcription factor CP2c has been recently validated as a promising target for development of novel anticancer therapy, its structure has not been solved yet. In the present study, the purified recombinant protein corresponding to the tetramerization domain of CP2c appeared to be well folded, whereas the Elf-1 domain showed a largely unfolded conformation. Particularly, the Elf-1 domain, which contains the putative DNA-binding region, showed a conformational equilibrium between relatively less-ordered and well-ordered conformers. Interestingly, addition of zinc shifted the equilibrium to the relatively more structured conformer, whereas zinc binding decreased the overall stability of the protein, leading to a promoted precipitation. Likewise, a dodecapeptide that has been suggested to bind to the Elf-1 domain also appeared to shift the conformational equilibrium and to destabilize the protein. These results constitute the first structural characterization of the CP2c domains and newly suggest that zinc ion might be involved in the conformational regulation of the protein.