HU Searches and Binds Specific DNA via a Multistep Process Combining Weak Electrostatic Binding, Protein Reorientation, and DNA Flexibility.

ABSTRACT: Despite their limited resolution, coarse-grained simulations have been the chosen method to obtain mechanistic information regarding the process of protein binding to DNA. Here, we demonstrate that state-of-the-art atomic simulations can capture binding events and provide new molecular insight. By using the bacterial model protein HU, we link existing crystal structures to the search and recognition states. We find that weak contacts mediated by only a few positively charged residues enable initial binding, followed by facilitated diffusion and transient rolling on DNA. Extended arms in the HU structure serve as antennae to search for DNA, permitting intrasegmental hops and intersegmental jumps. The transition to specific binding only occurs at the DNA target site, helped by its bendabilit

SUBMITTER: Chan EW 

PROVIDER: S-EPMC12569673 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature