DNA-Protein Cooperative Binding through Long-Range Elastic Coupling

TL;DR

This paper proposes a mechanical model where DNA elasticity mediates long-range cooperative binding of proteins, influenced by tension, DNA bending, and local stiffness changes, affecting protein interactions without direct contact.

Contribution

It introduces a tension-mediated elastic coupling mechanism for DNA-protein cooperativity, highlighting how mechanical properties of DNA influence protein interactions at a distance.

Findings

Tension controls the strength and range of protein-protein interactions.

Protein binding induces DNA bending and stiffness changes.

Interactions can be attractive or repulsive depending on orientation.

Abstract

Cooperativity plays an important role in the action of proteins bound to DNA. A simple, mechanical mechanism for cooperativity, in the form of a tension-mediated interaction between proteins bound to DNA at two different locations is proposed. These proteins are not in direct physical contact. DNA segments intercalating bound proteins are modeled as a Worm-Like Chain, which is free to deform in two dimensions. The tension-controlled protein-protein interaction is the consequence of two effects produced by the protein binding. The first is the introduction of a bend in the host DNA and the second is the modification of the bending modulus of the DNA in the immediate vicinity of the bound protein. The interaction between two bound proteins may be either attractive or repulsive, depending on their relative orientation on the DNA. Applied tension controls both the strength and the range of protein-protein interactions in this model. Properties of the cooperative interaction are discussed, along with experimental implications.