Sequence-Modulated Electrostatics Of Poly-Peptides-Dna Interactions

Unstructured poly-peptides are abundant in biology, either alone as intrinsically disordered peptides or as flexible domains of functional proteins. One example is the family of histone tails which are poly-cationic, unstructured terminal domains protruding from the nucleosome. Capable of acting as counter-ions to negatively charged DNA, histone tails are known to interact with nucleosomal DNA, linker DNA, as well as the nucleosome core. With the goal to gain first insights into the nature of peptide-nucleic acids interactions in a biological context, here we quantify and codify the interactions between histone tails and DNA, by employing the osmotic stress method to determine the force-spacing relations of ordered DNA arrays. Remarkably, such DNA force-spacing curves sensitively depend on both total peptide charge and the biochemical sequence of peptides with the same total charge, evidencing both charge regulated and sequence/structure dependent interactions between histone tails and DNA. We speculate on the physics of histone tail-DNA interactions in terms of charge patterns and structural compliance, and further discuss the biological implications of our observations and the general functional roles of poly-peptides in nucleic acids structure, interaction, and assembly.