Probing Allostery Through DNA

TLDR

Allostery is well documented for proteins but less recognized for DNA–protein interactions. The study shows that a protein’s binding to DNA is strongly modulated by a neighboring protein, with free‑energy oscillations of ~10 bp periodicity and ~15 bp decay, and that this DNA‑allosteric effect influences gene expression in bacteria and transcription‑factor affinity near nucleosomes, likely via helix deformation.

Abstract

Allostery is well documented for proteins but less recognized for DNA-protein interactions. Here, we report that specific binding of a protein on DNA is substantially stabilized or destabilized by another protein bound nearby. The ternary complex's free energy oscillates as a function of the separation between the two proteins with a periodicity of ~10 base pairs, the helical pitch of B-form DNA, and a decay length of ~15 base pairs. The binding affinity of a protein near a DNA hairpin is similarly dependent on their separation, which-together with molecular dynamics simulations-suggests that deformation of the double-helical structure is the origin of DNA allostery. The physiological relevance of this phenomenon is illustrated by its effect on gene expression in live bacteria and on a transcription factor's affinity near nucleosomes.