Enthalpic factors override the polyelectrolyte effect in the binding of EGR1 transcription factor to DNA

David C. Mikles, Vikas Bhat, Brett J. Schuchardt, Caleb B. McDonald, Amjad Farooq

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Protein-DNA interactions are highly dependent upon salt such that the binding affinity precipitously decreases with increasing salt concentration in a phenomenon termed as the polyelectrolyte effect. In this study, we provide evidence that the binding of early growth response (EGR) 1 transcription factor to DNA displays virtually zero dependence on ionic strength under physiological salt concentrations and that such feat is accomplished via favorable enthalpic contributions. Importantly, we unearth the molecular origin of such favorable enthalpy and attribute it to the ability of H382 residue to stabilize the EGR1-DNA interaction via both intermolecular hydrogen bonding and van der Waals contacts against the backdrop of salt. Consistent with this notion, the substitution of H382 residue with other amino acids faithfully restores salt-dependent binding of EGR1 to DNA in a canonical fashion. Remarkably, H382 is highly conserved across other members of the EGR family, implying that changes in bulk salt concentration are unlikely to play a significant role in modulating protein-DNA interactions central to this family of transcription factors. Taken together, our study reports the first example of a eukaryotic protein-DNA interaction capable of overriding the polyelectrolyte effect.

Original languageEnglish
Pages (from-to)82-91
Number of pages10
JournalJournal of Molecular Recognition
Volume27
Issue number2
DOIs
StatePublished - Feb 1 2014

Fingerprint

Early Growth Response Protein 1
Salts
DNA
Proteins
Hydrogen Bonding
Osmolar Concentration
Polyelectrolytes
Transcription Factors
Amino Acids
Growth

Keywords

  • hydrogen bonding
  • polyelectrolyte effect
  • Protein-DNA thermodynamics
  • salt tolerance
  • van der Waals contacts

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Enthalpic factors override the polyelectrolyte effect in the binding of EGR1 transcription factor to DNA. / Mikles, David C.; Bhat, Vikas; Schuchardt, Brett J.; McDonald, Caleb B.; Farooq, Amjad.

In: Journal of Molecular Recognition, Vol. 27, No. 2, 01.02.2014, p. 82-91.

Research output: Contribution to journalArticle

Mikles, David C. ; Bhat, Vikas ; Schuchardt, Brett J. ; McDonald, Caleb B. ; Farooq, Amjad. / Enthalpic factors override the polyelectrolyte effect in the binding of EGR1 transcription factor to DNA. In: Journal of Molecular Recognition. 2014 ; Vol. 27, No. 2. pp. 82-91.
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