Abstract
Among other effects, post-translational modifications (PTMs) have been shown to exert their function via the modulation of protein-protein interactions. For twelve different main PTM-types and associated subtypes and across 9 diverse species, we investigated whether particular PTM-types are associated with proteins with specific and possibly “strategic” placements in the network of all protein interactions by determining informative network-theoretic properties. 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. PTM-type-specific protein interaction network (PIN) properties can be rationalized with regard to the function of the respective PTM-carrying proteins. 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.
Highlights
As chief actors within living cells, proteins serve diverse functions such as catalysis, transport, structural building material and many others [1]
We tested whether specific post-translational modifications (PTMs)-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
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
Summary
As chief actors within living cells, proteins serve diverse functions such as catalysis, transport, structural building material and many others [1]. More than 200 different types of PTMs have been identified that affect many aspects of cellular functionalities, such as metabolism, signal transduction, and protein stability [4, 5]. These modifications include phosphorylation, glycosylation, methylation, acetylation, amidation and many other types, see http://www.uniprot.org/docs/ptmlist for a more detailed controlled vocabulary of PTMs curated by UniProt [6]. Several databases have been established to store the obtained information, such as UniProt [8], dbPTM [9], PTMCuration [10], PTMcode [11] and many others. A number species-specific databases have been developed [12,13,14] offering the opportunity to investigate PTMs in an evolutionary context as well
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
