Predicting the mechanism and rate of H-NS binding to AT-rich DNA

摘要

Author summary The Histone-like Nucleoid Structuring protein (H-NS) occurs in enterobacteria, such as Salmonella typhimurium and Escherichia coli, and structures DNA by forming filaments along DNA duplexes. Several nucleotide sequences have been identified to which H-NS binds with high affinity. Yet, obtaining highly detailed structural information of the H-NS DNA complex has proven to be a major challenge, which has not been yet resolved. By employing molecular dynamics simulations we were able to provide high resolution insights into the mechanism of DNA binding by H-NS. We identified various ways in which H-NS can bind to DNA. In all binding events, a conserved region in the protein initiates the association of H-NS to DNA. Our results show that H-NS binds in the minor groove of AT-rich DNA via a series of intermediate steps. Using advanced molecular simulation methods we predicted that the process of H-NS binding to the DNA backbone to full insertion into the minor groove occurs in the order of a million times per second, which is slower than the non-specific association of H-NS to the DNA backbone.