Intersegment Transfer and the Dynamical Architecture of Fis Protein–DNA Multimer Complexes

Gene regulation often entails a cooperative dynamic interplay among several protein molecules and several distinct DNA segments. Intersegment transfer of the Fis protein stimulates DNA inversion during DNA recombination. Individual DNA segments have been found to facilitate the dissociation of Fis proteins already bound to DNA and also allow for the transfer of the Fis between segments. Here, we use the hybrid coarse-grained AWSEM/3SPN.2C model to simulate the Fis protein intersegment transfer and explore its mechanism. We show that entropic effects within the Fis protein–DNA complex dictate the transfer pathway through specific structural configurations, involving specific grooves and consequent orientation constraints on the DNA segments. Multiple copies of the Fis protein facilitate intersegment transfer, explaining how changes in protein–DNA stoichiometry and concentration influence how the Fis–DNA complex architecture is established. This orientational dependence indicates that the assembly of the Fis–DNA complex mimics the interlocking of screws, functioning as a molecular machine that may couple to DNA supercoiling and torsional stress in the DNA generated by motor proteins, thus offering a potential regulatory mechanism for chromosomal organization and gene expression.