Evidence that the bZIP domains of the Jun transcription factor bind to DNA as monomers prior to folding and homodimerization

Kenneth L. Seldeen, Caleb B. McDonald, Brian J. Deegan, Amjad Farooq

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The Jun oncoprotein belongs to the AP1 family of transcription factors that is collectively engaged in diverse cellular processes by virtue of their ability to bind to the promoters of a wide spectrum of genes in a DNA sequence-dependent manner. Here, using isothermal titration calorimetry, we report detailed thermodynamics of the binding of bZIP domain of Jun to synthetic dsDNA oligos containing the TRE and CRE consensus promoter elements. Our data suggest that binding of Jun to both sites occurs with indistinguishable affinities but with distinct thermodynamic signatures comprised of favorable enthalpic contributions accompanied by entropic penalty at physiological temperatures. Furthermore, anomalously large negative heat capacity changes observed provoke a model in which Jun loads onto DNA as unfolded monomers coupled with subsequent folding and homodimerization upon association. Taken together, our data provide novel insights into the energetics of a key protein-DNA interaction pertinent to cellular signaling and cancer. Our study underscores the notion that the folding and dimerization of transcription factors upon association with DNA may be a more general mechanism employed in protein-DNA interactions and that the conventional school of thought may need to be re-evaluated.

Original languageEnglish
Pages (from-to)75-84
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume480
Issue number2
DOIs
StatePublished - Dec 15 2008

Fingerprint

Transcription Factors
Monomers
DNA
Thermodynamics
Association reactions
Cell signaling
Calorimetry
Dimerization
Oncogene Proteins
DNA sequences
Titration
Specific heat
Proteins
Hot Temperature
Genes
Temperature
Neoplasms

Keywords

  • Basic leucine zipper bZIP
  • DNA promoter elements TRE and CRE
  • Isothermal titration calorimetry
  • Jun Transcription factor
  • Protein-DNA thermodynamics

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Evidence that the bZIP domains of the Jun transcription factor bind to DNA as monomers prior to folding and homodimerization. / Seldeen, Kenneth L.; McDonald, Caleb B.; Deegan, Brian J.; Farooq, Amjad.

In: Archives of Biochemistry and Biophysics, Vol. 480, No. 2, 15.12.2008, p. 75-84.

Research output: Contribution to journalArticle

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