Among other effects, post-translational modifications PTMs have been shown to exert their function via the modulation of protein-protein interactions. Proteins undergoing a PTM were observed to engage in more interactions and positioned in more central locations than non-PTM proteins.
Among the twelve considered PTM-types, phosphorylated proteins were identified most consistently as being situated in central network locations and with the broadest interaction spectrum to proteins carrying other PTM-types, while glycosylated proteins are preferentially located at the network periphery. For the human interactome, proteins undergoing sumoylation or proteolytic cleavage were found with the most characteristic network properties.
For example, glycosylation sites were found enriched in proteins with plasma membrane localizations and transporter or receptor activity, which generally have fewer interacting partners. The involvement in disease processes of human proteins undergoing PTMs was also found associated with characteristic PIN properties. By integrating global protein interaction networks and specific PTMs, our study offers a novel approach to unraveling the role of PTMs in cellular processes.
The function of proteins is frequently modulated by chemical modifications introduced after translation from RNA. These post-translational modifications PTMs have been shown to also influence the interaction between proteins carrying them. We tested whether specific PTM-types characterized by attaching different chemical groups are associated with proteins with characteristic and possibly strategic positions within the network of all protein interactions in cellular systems.
Based on network-theoretic analyses of PTMs in the context of protein interaction networks of nine selected species, we indeed observed distinctive properties of twelve PTM-types tested. Phosphorylation was found associated with proteins in central locations with the broadest interaction scope, while glycosylation was more prominent in proteins at the periphery of the web of all protein interactions. The involvement in disease processes of human proteins undergoing PTMs was also found associated with characteristic protein interaction network properties.
