3.1.2. Post-Translational Modifications

Because of their accessibility to modifying enzymes, IDPs are frequent targets for post-translational modifications (PTMs), which expand their functional versatility [185,199]. The occurrence of PTMs causes structural changes on IDPs by affecting their energy landscapes, due to modifications of the physicochemical properties of the primary sequence [185]. Post-translational modifications engage in the addition of chemical functional groups (usually small radicals such as phosphoryl, alkyl, acyl or glycosyl) or involve the direct modification of residues through reactions of oxidation, deimidation, and deamidation. Intrinsically disordered proteins suffering PTMs may have their electrostatic, steric, and hydrophobic properties modified, possibly inducing transformations on the structure due to enhancement/inhibition of contacts of motifs within the IDP chain or with binding partners [185,200–202]. Phosphorylation is one of the most prevalent PTM and constitutes a major regulatory mechanism in various cellular processes involving signal transduction. Replacing a neutral hydroxyl group with a tetrahedral phosphoryl results in new possibilities for intra- and intermolecular electrostatic interactions (e.g., salt bridges and hydrogen bonds). Many other types of PTMs work in a similar fashion (but modulating different chemical properties), providing new forms of interaction that can ultimately cause alterations in IDPs activity, including disordered to ordered transitions.
