BIOPHYSICAL THEORY AND MODELING |
Salt-Mediated Electrostatics in the Association of TATA Binding Proteins to DNA: A Combined Molecular Mechanics/Poisson-Boltzmann Study
Johan Bredenberg 1, Cristina Russo 1 and Marcia O Fenley 1*
1 Florida State University
* To whom correspondence should be addressed. E-mail: mfenley{at}sb.fsu.edu.
Submitted on November 14, 2007
Revised on December 17, 2007
Accepted on 30 January 2008
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Abstract |
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The TATA-Binding Protein (TBP) is a key component of the archaea ternary preinitiation transcription assembly. The archaeon TBP from the halophile/hyperthermophile organism Pyrococcus woesei (Pw) is adapted to high concentrations of salt and high temperature environments. Although most eukaryotic TBPs are mesophilic and adapted to physiological conditions of temperature and salt, they are very similar to their halophilic counterparts in sequence and fold. However, while the binding affinity to DNA of halophilic TBPs increase with increasing salt concentrations, the opposite is observed for mesophilic TBPs. We investigated these differences in salt dependent non-specific DNA-binding behavior of halophilic and mesophilic TBPs, by using a combined Molecular Mechanics/Poisson-Boltzmann approach. Our results are qualitatively in good agreement with experimentally observed salt dependent DNA-binding for mesophilic and halophilic TBPs, and suggest that the distribution and the total number of charged residues may be the main underlying contributor in the association process. Therefore, the difference in the salt dependent binding behavior of mesophilic and halophilic TBPs to DNA may be due to the very unique charge and potential distribution of both TBPs, which consequently alters the number of repulsive and attractive electrostatic interactions.
Key Words:
DNA, Poisson-Boltzmann equation, TATA-binding proteins, electrostatics, molecular mechanics, salt dependence
