Structural Basis of Enhanced Facilitated Diffusion of DNA-Binding Protein in Crowded Cellular Milieu.

Structural Basis of Enhanced Facilitated Diffusion of DNA-Binding Protein in Crowded Cellular Milieu. Biophys J. 2019 Nov 29;: Authors: Dey P, Bhattacherjee A Abstract Although the fast association between DNA-binding proteins (DBPs) and DNA is explained by a facilitated diffusion mechanism, in which DBPs adopt a weighted combination of three-dimensional diffusion and one-dimensional (1D) sliding and hopping modes of transportation, the role of cellular environment that contains many nonspecifically interacting proteins and other biomolecules is mostly overlooked. By performing large-scale computational simulations with an appropriately tuned model of protein and DNA in the presence of nonspecifically interacting bulk and DNA-bound crowders (genomic crowders), we demonstrate the structural basis of the enhanced facilitated diffusion of DBPs inside a crowded cellular milieu through, to our knowledge, novel 1D scanning mechanisms. In this one-dimensional scanning mode, the protein can float along the DNA under the influence of nonspecific interactions of bulk crowder molecules. The search mode is distinctly different compared to usual 1D sliding and hopping dynamics in which protein diffusion is regulated by the DNA electrostatics. In contrast, the presence of genomic crowders expedites the target search process by transporting the protein over DNA segments through the formation of a transient protein-crowder bridged complex. By analyz...
Source: Biophysical Journal - Category: Physics Authors: Tags: Biophys J Source Type: research