pH modulates the binding of early growth response protein 1 transcription factor to DNA

摘要: The transcription factor early growth response protein (EGR)1 orchestrates a plethora of signaling cascades involved in cellular homeostasis, and its downregulation has been implicated the development prostate cancer. Herein, using battery biophysical tools, we show that binding EGR1 to DNA is tightly regulated by solution pH. Importantly, affinity undergoes an enhancement more than order magnitude with increase pH from 5 8, implying deprotonation ionizable residue accounts for such behavior. This identified as His382 virtue fact replacement nonionizable residues abolishes dependence DNA. Notably, inserts into major groove DNA, stabilizes EGR1-DNA interaction via both hydrogen bonding van der Waals contacts. Remarkably, mainly conserved across other members EGR family, histidine protonation-deprotonation may serve molecular switch modulating protein-DNA interactions are central this family factors. Collectively, our findings reveal unexpected but key step recognition factors, suggest they act sensors within intracellular environment.