투고논문

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

Ku-Sung Jo1,†, Ki-Sung Ryu1,†, Hee-Wan Yu1,¶, Seu-Na Lee1,§, Ji-Hun Kim2, Eun-Hee Kim3, Chae-Yeon Wang1, Chan-Gil Kim1, Chul Geun Kim4, and Hyung-Sik Won1,*

1 Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju, Chungbuk 27478, Republic of Korea
2 College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea
3 Protein Structure Group, Korea Basic Science Institute, Ochang, Chungbuk 28119, Republic of Korea
4 Department of Life Science and Research Institute for Natural Sciences, College of Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea

Received Dec 1, 2018; Revised Dec 13, 2018; Accepted Dec 14, 2018

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.

† These authors contributed equally to this work
¶ Current address: R&D center, TiumBio Co. Ltd., Seongnam, Gyeonggi 13493, Republic of Korea
§ Current address: Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea
* Address correspondence to: Hyung-Sik Won, Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju, Chungbuk 27478, Republic of Korea; Tel: 82-43-840-3589; E-mail: wonhs@kku.ac.kr