Journal article
Electrostatic effects in homeodomain-DNA interactions
Journal of molecular biology, Vol.267(2), pp.368-381
1997
DOI: 10.1006/jmbi.1996.0842
PMID: 9096232
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(Δ
C
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.
Details
- Title: Subtitle
- Electrostatic effects in homeodomain-DNA interactions
- Creators
- F Fogolari - Dipartimento di Scienze e Tecnologie Biomediche Università di Udine, Via Gervasutta, 48-33100 Udine, ItalyA.H Elcock - Department of Chemistry and Biochemistry, Urey Hall 4238 University of California at San Diego, La Jolla, CA 92093-0365, USAG Esposito - Dipartimento di Scienze e Tecnologie Biomediche Università di Udine, Via Gervasutta, 48-33100 Udine, ItalyP Viglino - Dipartimento di Scienze e Tecnologie Biomediche Università di Udine, Via Gervasutta, 48-33100 Udine, ItalyJ.M Briggs - Department of Chemistry and Biochemistry, Urey Hall 4238 University of California at San Diego, La Jolla, CA 92093-0365, USAJ.A McCammon - Department of Chemistry and Biochemistry, Urey Hall 4238 University of California at San Diego, La Jolla, CA 92093-0365, USA
- Resource Type
- Journal article
- Publication Details
- Journal of molecular biology, Vol.267(2), pp.368-381
- Publisher
- Elsevier Ltd
- DOI
- 10.1006/jmbi.1996.0842
- PMID
- 9096232
- ISSN
- 0022-2836
- eISSN
- 1089-8638
- Language
- English
- Date published
- 1997
- Academic Unit
- Physics and Astronomy; Biochemistry and Molecular Biology
- Record Identifier
- 9984024405502771
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