Mechanisms of DNA-mediated allostery

Midas Segers, Aderik Voorspoels, Takahiro Sakaue, Enrico Carlon

Published 2023-05-06Version 1

Proteins often regulate their activities via allostery - or action at a distance - in which the binding of a ligand at one binding site influences the affinity for another ligand at a distal site. Although less studied than in proteins, allosteric effects have been observed in experiments with DNA as well. In these experiments two or more proteins bind at distinct DNA sites and interact indirectly with each other, via a mechanism mediated by the linker DNA molecule. We develop a mechanical model of DNA/protein interactions which predicts three distinct mechanisms of allostery. Two of these involve an enthalphy-mediated allostery, while a third mechanism is entropy driven. We analyze experiments of DNA allostery and highlight the distinctive signatures allowing one to identify which of the proposed mechanisms best fits the data.