Asymmetric DNA-Search Dynamics by Symmetric Dimeric
Proteins
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Abstract
We focus on dimeric DNA-binding proteins
from two well-studied
families: orthodox type II restriction endonucleases (REs) and transcription
factors (TFs). Interactions of the protein’s recognition sites
with the DNA and, particularly, the contribution of each of the monomers
to one-dimensional (1D) sliding along nonspecific DNA were studied
using computational tools. Coarse-grained molecular dynamics simulations
of DNA scanning by various TFs and REs provide insights into how the
symmetry of a homodimer can be broken while they nonspecifically interact
with DNA. The characteristics of protein sliding along DNA, such as
the average sliding length, partitioning between 1D and 3D search,
and the one-dimensional diffusion coefficient <i>D</i><sub>1</sub>, strongly depend on the salt concentration, which in turn
affects the probability of the two monomers adopting a cooperative
symmetric sliding mechanism. Indeed, we demonstrate that maximal DNA
search efficiency is achieved when the protein adopts an asymmetric
search mode in which one monomer slides while its partner hops. We
find that proteins classified as TFs have a higher affinity for the
DNA, longer sliding lengths, and an increased probability of symmetric
sliding in comparison with REs. Moreover, TFs can perform their biological
function over a much wider range of salt concentrations than REs.
Our results demonstrate that the different biological functions of
DNA-binding proteins are related to the different nonspecific DNA
search mechanisms they adopt