Molecular Mechanism of Facilitated Dissociation of Fis Protein from DNA.

Fis protein is a nucleoid-associated protein that plays many roles in transcriptional regulation and DNA site-specific recombination. In contrast to the naïve expectation based on stoichiometry, recent single-molecule studies have shown that the dissociation of Fis protein from DNA is accelerated by increasing the concentration of the Fis protein. Because the detailed molecular mechanism of facilitated dissociation is still not clear, in this study, we employ computational methods to explore the binding landscapes of Fis:DNA complexes with various stoichiometries. When two Fis molecules are present, simulations uncover a ternary complex, where the originally bound Fis protein is partially dissociated from DNA. The simulations support a three-state sequential kinetic model (N ⇄ I → D) for facilitated dissociation, thus explaining the concentration-dependent dissociation.