Systematic identification of phosphorylation-mediated protein interaction switches

PLoS Comput Biol. 2017 Mar 27;13(3):e1005462. doi: 10.1371/journal.pcbi.1005462. eCollection 2017 Mar.

Abstract

Proteomics techniques can identify thousands of phosphorylation sites in a single experiment, the majority of which are new and lack precise information about function or molecular mechanism. Here we present a fast method to predict potential phosphorylation switches by mapping phosphorylation sites to protein-protein interactions of known structure and analysing the properties of the protein interface. We predict 1024 sites that could potentially enable or disable particular interactions. We tested a selection of these switches and showed that phosphomimetic mutations indeed affect interactions. We estimate that there are likely thousands of phosphorylation mediated switches yet to be uncovered, even among existing phosphorylation datasets. The results suggest that phosphorylation sites on globular, as distinct from disordered, parts of the proteome frequently function as switches, which might be one of the ancient roles for kinase phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Computer Simulation
  • Models, Chemical*
  • Models, Molecular
  • Phosphorylation
  • Phosphotransferases / chemistry*
  • Phosphotransferases / ultrastructure
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Mapping / methods*
  • Proteome / chemistry*
  • Proteome / ultrastructure
  • Sequence Analysis, Protein / methods*
  • Structure-Activity Relationship

Substances

  • Proteome
  • Phosphotransferases