Electrostatic effects in homeodomain-DNA interactions

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,...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular biology 1997-03, Vol.267 (2), p.368-381
Main Authors: Fogolari, F, Elcock, A.H, Esposito, G, Viglino, P, Briggs, J.M, McCammon, J.A
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Base Sequence
Chemical Phenomena
Chemistry, Physical
DNA - metabolism
DNA-binding proteins
DNA-Binding Proteins - metabolism
Electrochemistry
electrostatics
homeodomain
Homeodomain Proteins - chemistry
Homeodomain Proteins - metabolism
Models, Molecular
Molecular Sequence Data
Mutation
Nucleic Acid Conformation
Poisson-Boltzmann
Protein Binding
Protein Conformation
protein-DNA interactions
Salts
Static Electricity
Temperature
Thermodynamics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-2836
1089-8638
DOI:10.1006/jmbi.1996.0842