Is the H4 histone tail intrinsically disordered or intrinsically multifunctional?

The structural versatility of histone tails is one of the key elements in the organisation of chromatin, which allows for the compact storage of genomic information. However, this structural diversity also complicates experimental and computational studies. Here, the potential and free energy landscape for the isolated and bound H4 histone tail are explored. The landscapes exhibit a set of distinct structural ensembles separated by high energy barriers, with little difference between isolated and bound tails. This consistency is a desirable feature that facilitates the formation of transient interactions, which are required for the liquid-like chromatin organisation. The existence of multiple, distinct structures on a multifunnel energy landscape is likely to be associated with multifunctionality, i.e. a set of evolved, distinct functions. Contrasting it with previously reported results for other disordered peptides, this type of landscape may be associated with a conformational selection based binding mechanism. Given the similarity to other systems exhibiting similar multifunnel energy landscapes, the disorder in histone tails might be better described in context of multifunctionality.