Effect of osmolytes on the binding of EGR1 transcription factor to DNA.

摘要: Osmolytes play a key role in maintaining protein stability and mediating macromolecular interactions within the intracellular environment of cell. Herein, we show that osmolytes such as glycerol, sucrose, polyethylene glycol 400 (PEG400) mitigate binding early growth response (protein) 1 (EGR1) transcription factor to DNA differential manner. Thus, while physiological concentrations glycerol only moderately reduce affinity, addition sucrose PEG400 is concomitant with loss affinity by an order magnitude. This salient observation suggests EGR1 most likely subject conformational equilibrium exert their effect via favorable unliganded conformation. Consistent this notion, our analysis reveals displays rather high structural complex DNA, conformation becomes significantly destabilized solution. In particular, liganded adopts well-defined arc-like architecture, samples comparatively large space between two distinct states periodically interconvert elongated rod-like shape on submicrosecond time scale. Consequently, ability favorably interact so stabilize it could account for negative osmotic stress EGR1-DNA interaction observed here. Taken together, study sheds new light modulating protein-DNA interaction.