DNA Internal Motion Likely Accelerates Protein Target Search in a Packed Nucleoid

Abstract

Transcription factors must diffuse through densely packed and coiled DNA to find their binding sites. Using a coarse-grained model of DNA and lac repressor (LacI) in the Escherichia coli nucleoid, simulations were performed to examine how LacI diffuses in such a space. Despite the canonical picture of LacI diffusing rather freely, in reality the DNA is densely packed, is not rigid but highly mobile, and the dynamics of DNA dictates to a great extent the LacI motion. A possibly better picture of unbound LacI motion is that of gated diffusion, where DNA confines LacI in a cage, but LacI can move between cages when hindering DNA strands move out of the way. Three-dimensional diffusion constants for unbound LacI computed from simulations closely match those for unbound LacI in vivo reported in the literature. The internal motions of DNA appear to be governed by strong internal forces arising from being crowded into the small space of the nucleoid. A consequence of the DNA internal motion is that protein target search may be accelerated.

Intracellular Positioning Systems Limit the Entropic Eviction of Secondary Replicons Toward the Nucleoid Edges in Bacterial Cells

“…Entropic unmixing might therefore limit the ability of a newly acquired replicon to find a target sequence for integration. In good agreement with this hypothesis it appeared that DNA internal motion likely accelerates protein target search in a packed nucleoid (Chow & Skolnick, 2017) Material and methods…”

How Important Is Protein Diffusion in Prokaryotes?

“…The nucleoid can become a barrier for larger, ribosome-sized, proteins or protein-aggregates that are too large to diffuse through the meshwork presented by the DNA (Figure 2E ) (Bakshi et al, 2012 ). In a model of LacI diffusion in the nucleoid it was concluded that DNA dynamics determines the motion of LacI to a large extent (Chow and Skolnick, 2017 ). During an osmotic upshift, next to the increased crowding, invaginations provide temporal barriers for proteins (Mika et al, 2010 ) until the cell recovers its volume and resumes growth.…”

Understanding Protein Mobility in Bacteria by Tracking Single Molecules

“…Binding of LacI can also be near specific (i.e., to sequences that are closely related to the cognate sequence, e.g., the lac operator in this case). To these interactions, one should also add the presence of chromosomal DNA motions within the nucleoid, which have been suggested to accelerate target search for DNA-binding proteins such as LacI [52] .…”