Stability and DNA-Binding Ability of the bZIP Dimers Formed by the ATF-2 and c-Jun Transcription Factors

• Published in: Journal of molecular biology 2010-02, Vol.396 (2), p.431-440
• Main Authors: Carrillo, R.J., Dragan, A.I., Privalov, P.L.
• Format: Article
• Language: English
• Subjects: Activating Transcription Factor 2 - chemistry; Activating Transcription Factor 2 - metabolism; Amino Acid Sequence; ATF2; Basic-Leucine Zipper Transcription Factors - chemistry; Basic-Leucine Zipper Transcription Factors - metabolism; bZIP; c-Jun; DNA - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; enhanceosome, DNA; Humans; Protein Binding; Protein Interaction Domains and Motifs; Protein Interaction Mapping; Protein Multimerization - physiology; Protein Stability; Proto-Oncogene Proteins c-jun - chemistry; Proto-Oncogene Proteins c-jun - metabolism; Transcription Factors - chemistry; Transcription Factors - metabolism
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2009.11.050

The dimer formed by the ATF-2 and c-Jun transcription factors is one of the main components of the human interferon-β enhanceosome. Although these two transcription factors are able to form two homodimers and one heterodimer, it is mainly the heterodimer that participates in the formation of this enhanceosome, binding specifically to the positive regulatory domain IV (PRDIV) site of the enhancer DNA. To understand this surprising advantage of the heterodimer, we investigated the association of these transcription factors using fragments containing the basic DNA-recognition segment and the basic leucine zipper domain (bZIP). It was found that the probability of forming the hetero-bZIP significantly exceeds the probability of forming homo-bZIPs, and that the hetero-bZIP interacts more strongly with the PRDIV site of the interferon-β enhancer, especially in the orientation that places the folded ATF-2 basic segment in the upstream half of this asymmetric site. The effect of salt on the formation of the ATF-2/c-Jun dimer and on its ability to bind the target PRDIV site showed that electrostatic interactions between the charged groups of these proteins and with DNA play an essential role in the formation of the asymmetric ATF-2/c-Jun/PRDIV complex.