Electrostatic effects in homeodomain-DNA interactions

F. Fogolari, A. H. Elcock, Gennaro Esposito, P. Viglino, J. M. Briggs, J. A. McCammon

Research output: Contribution to journalArticle

Abstract

We report here an investigation of the role of electrostatics in homeodomain-DNA interactions using techniques based around the use of the Poisson-Boltzmann equation. In the present case such a study is of particular interest, since in contrast to other proteins previously studied with this method, the homeodomain is a small, highly charged protein that forms extensive ion pairs upon binding DNA. We have investigated the salt dependence of the binding constant for specific association and for a variety of models for non-specific association. The results indicate that, in line with the models proposed by Manning and Record, the entropy of counterion release accounts for a significant fraction of the salt dependence of the binding free energy, though this is perhaps due to fortuitous cancellation of other contributing terms. The thermodynamic effects of a number of specific homeodomain mutants were also investigated, and partly rationalized in terms of favorable electrostatic interactions in the major goove of DNA. Investigation of the temperature-dependence of the free energy of association indicates that the electrostatic contributions become increasingly favorable as the temperature rises. For this particular system, however, there appears to be no significant electrostatic contribution to the Δ(ΔC(p)) of association. Finally, an analysis of the free energy of interaction when the homeodomain is moved ca one Debye length from the DNA suggests that pure electrostatic forces are able to steer the homeodomain into a partially correct orientation for binding to the DNA.

Original languageEnglish (US)
Pages (from-to)368-381
Number of pages14
JournalJournal of Molecular Biology
Volume267
Issue number2
DOIs
StatePublished - Mar 28 1997

Fingerprint

Static Electricity
DNA
Salts
Free Association
Temperature
Entropy
Thermodynamics
Proteins
Ions

Keywords

  • DNA-binding proteins
  • Electrostatics
  • Homeodomain
  • Poisson-Boltzmann
  • Protein-DNA interactions

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Fogolari, F., Elcock, A. H., Esposito, G., Viglino, P., Briggs, J. M., & McCammon, J. A. (1997). Electrostatic effects in homeodomain-DNA interactions. Journal of Molecular Biology, 267(2), 368-381. https://doi.org/10.1006/jmbi.1996.0842

Electrostatic effects in homeodomain-DNA interactions. / Fogolari, F.; Elcock, A. H.; Esposito, Gennaro; Viglino, P.; Briggs, J. M.; McCammon, J. A.

In: Journal of Molecular Biology, Vol. 267, No. 2, 28.03.1997, p. 368-381.

Research output: Contribution to journalArticle

Fogolari, F, Elcock, AH, Esposito, G, Viglino, P, Briggs, JM & McCammon, JA 1997, 'Electrostatic effects in homeodomain-DNA interactions', Journal of Molecular Biology, vol. 267, no. 2, pp. 368-381. https://doi.org/10.1006/jmbi.1996.0842
Fogolari F, Elcock AH, Esposito G, Viglino P, Briggs JM, McCammon JA. Electrostatic effects in homeodomain-DNA interactions. Journal of Molecular Biology. 1997 Mar 28;267(2):368-381. https://doi.org/10.1006/jmbi.1996.0842
Fogolari, F. ; Elcock, A. H. ; Esposito, Gennaro ; Viglino, P. ; Briggs, J. M. ; McCammon, J. A. / Electrostatic effects in homeodomain-DNA interactions. In: Journal of Molecular Biology. 1997 ; Vol. 267, No. 2. pp. 368-381.
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