The effects of viral nucleosome-like particles on DNA compaction, dynamics, and accessibility.

Abstract

Melbourne viruses are large DNA-based viruses that organize their genome using histone-like proteins that act as “fused” histones with homologies similar to the histone dimers found in eukaryotic nucleosomes. Cryo-EM studies have suggested that these viral nucleosome-like particles have a weak binding affinity that causes their wrapped DNA structure to have more open conformations than their eukaryotic counterparts. However, these studies provide limited insight into the dynamics and stability of the DNA in these viral structures and do not reveal how differences between the viral and eukaryotic histone-like proteins affect large-scale structural properties such as DNA unwrapping, DNA accessibility, and protein core stability. To probe the dynamical differences between the eukaryotic nucleosome and viral nucleosome-like particle and whether this equally affects differing DNA types, we have performed a series of all-atom molecular dynamics simulations on nucleosome systems with different protein core and DNA sequences. Our results show that differences between the viral and eukaryotic structures create weaker overall stability of the viral system and promote DNA breathing and oscillations of the DNA ends around the protein core regardless of DNA composition. While the presence of normal histone tails adds to nucleosome stability, replacing eukaryotic histone tails with viral histone connectors also creates a more dynamic and unstable system. Together, our results show that the evolutionarily diverse mechanisms of compacting DNA in eukaryotic and viral systems result in disparate DNA compaction and accessibility in these systems.