Elliot Chan

Publications

DNA bending proteins vs supercoiling

Watson et al. investigate the active role DNA can play in protein-DNA interactions via supercoiling and how it affects how IHF plays it's architectural roles.

Table of Contents

The integration host factor (IHF) is a prominent example of indirect readout as it imposes one of the strongest bends on relaxed linear DNA. However, the relation between IHF and torsionally constrained DNA, as occurs physiologically, remains unclear. By using atomistic molecular dynamics simulations on DNA minicircles, we reveal, for the first time, the reciprocal influence between a DNA-bending protein and supercoiling. While the increased curvature of supercoiled DNA enhances wrapping around IHF, the protein pins the position of plectonemes, organizing the topology of the loop in a unique and specific manner. In addition, IHF restrains under- or overtwisted DNA depending on whether the complex is formed in negatively or positively supercoiled DNA. This effectively enables IHF to become a ‘supercoiling buffer’ that dampens changes in the surrounding superhelical stress through DNA breathing around the protein or complex dissociation. We finally provide evidence of DNA bridging by IHF and reveal that these bridges divide DNA into independent topological domains. We anticipate that the crosstalk detected here between the ‘active’ DNA and the multifaceted IHF could be common to other DNA-protein complexes relying on the deformation of DNA.

GD Watson, EW Chan, MC Leake, A Noy (2022) “Structural interplay between DNA-shape protein recognition and supercoiling: the case of IHF” Comput Struct Biotech J, 20, 5264-5274 doi:10.1016/j.csbj.2022.09.020