Structural analysis of mammalian protein phosphorylation at a proteome level

Abstract

Phosphorylation is an essential post-translational modification for almost all cellular processes. Several global phosphoproteomics analyses have revealed phosphorylation profiles under different conditions. Beyond identification of phospho-sites, protein structures add another layer of information about their functionality. In this study, we systematically characterize phospho-sites based on their 3D locations in the protein and establish a location map for phospho-sites. More than 250,000 phospho-sites have been analyzed, of which 8,686 sites match at least one structure and are stratified based on their respective 3D positions. Core phospho-sites possess two distinct groups based on their dynamicity. Dynamic core phosphorylations are significantly more functional compared with static ones. The dynamic core and the interface phosphosites are the most functional among all 3D phosphorylation groups. Our analysis provides global characterization and stratification of phospho-sites from a structural perspective that can be utilized for predicting functional relevance and filtering out false positives in phosphoproteomic studies.