Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
New Insights on Non-specific Protein-DNA Interactions: the DNase I Model
In the cell, DNA interacts almost continuously with proteins in order to ensure its biological functions. Specific and non-specific protein-DNA interactions imply the formation of intermolecular interfaces requiring electrostatic and structural complementarity of the related partners. Nevertheless, the mechanisms underlying the formation of non-specific protein-DNA complexes remain particularly obscure.
In this context, we chose to study the DNase I/DNA system as a representative and rather simple model of non-specific complex. DNase I is a glycoprotein which hydrolyzes the DNA phosphodiester linkages in presence of divalent cations, Ca2+ and Mg2+, and its activity depends on the DNA sequence.
Combining various experimental and theoretical techniques, we study DNA oligomers and DNase I, free and bound. We demonstrate that Ca2+ and Mg2+ are crucial for optimizing the electrostatic fit between DNA and enzyme. Preferential DNase I cleavages are found to be correlated to enhanced DNA dynamics that allow to minimize the cost of DNA deformation upon binding. Overall, this work highlights that the structure/function relationship in non-specific DNA-protein interaction parallels many features observed for specific DNA-protein recognition mechanisms.