Sequence-based prediction of the effects of histones H1 post-translational modifications: impact on the features related to the function

Abstract

Post-translational modifications modulate histones H1 activity but their impact on proteins features was not studied so far. Therefore, this work was intended to answer how the most common modifications, i.e. acetylation, methylation, phosphorylation and ubiquitination, can influence on histones H1 to alter their physicochemical and molecular properties. Investigations were done with the use of sequence-based predictors trained on various protein features. Because a full set of histones H1 modifications is not included in the databases of histone proteins, the survey was performed on the human, animals, plants, fungi and protist sequences selected from UniProtKB/Swiss-Prot database. Quantitative proportions of modifications were similar between the groups of organisms (CV = 0.11) but different within the group (p < 0.05). The effects of modifications were evaluated with the use of mutated sequences obtained through the substitution of modified residue of Lys, Ser and Thr by a neutral residue of the Ala. An advantage of deleterious mutations at the sites of acetylation, methylation and ubiquitination over the sites of phosphorylation (p < 0.05) indicate that this modification have more redundant character. Modifications evoke an increase of protein solubility and stability as well as acceleration of folding kinetics and a weaken of binding affinity. Besides, they also maintain a higher extent of intrinsic structural disorder. The obtained results prove that modifications should be perceived as relevant factors influencing physicochemical features determining molecular properties. Thus, histones H1 functioning is strictly correlated with the status of modifications. Communicated by Ramaswamy H. Sarma