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Energetic coupling along an allosteric communication channel drives the binding of Jun‐Fos heterodimeric transcription factor to DNA
Author(s) -
Seldeen Kenneth L.,
Deegan Brian J.,
Bhat Vikas,
Mikles David C.,
McDonald Caleb B.,
Farooq Amjad
Publication year - 2011
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2011.08124.x
Subject(s) - allosteric regulation , transcription factor , isothermal titration calorimetry , dna , biology , computational biology , zipper , mutagenesis , cooperative binding , protein–dna interaction , biophysics , dna binding protein , protein–protein interaction , binding site , genetics , chemistry , biochemistry , mutation , gene , computer science , algorithm , receptor
Although allostery plays a central role in driving protein–DNA interactions, the physical basis of such cooperative behavior remains poorly understood. In the present study, using isothermal titration calorimetry in conjunction with site‐directed mutagenesis, we provide evidence that an intricate network of energetically‐coupled residues within the basic regions of the Jun‐Fos heterodimeric transcription factor accounts for its allosteric binding to DNA. Remarkably, energetic coupling is prevalent in residues that are both close in space, as well as residues distant in space, implicating the role of both short‐ and long‐range cooperative interactions in driving the assembly of this key protein–DNA interaction. Unexpectedly, many of the energetically‐coupled residues involved in orchestrating such a cooperative network of interactions are poorly conserved across other members of the basic zipper family, emphasizing the importance of basic residues in dictating the specificity of basic zipper–DNA interactions. Collectively, our thermodynamic analysis maps an allosteric communication channel driving a key protein–DNA interaction central to cellular functions in health and disease.