Simulating mono- and multiprotein phosphorylation within nanoclusters.

Abstract

Protein nanoclustering is a characteristic feature of their activated state and is essential for forming numerous subcellular structures. The formation of these nanoclusters is highly dependent on a series of posttranslational modifications, such as mono- and multiphosphorylation and dephosphorylation of residues. We theoretically simulate how a protein can be either mono- or multiphosphorylated on several residues in functional nanoclusters, depending on effective biophysical parameters (diffusion, dwell time, etc.). Moving beyond a binary view of phosphorylation, this approach highlights the interplay between mono- and multiphosphorylation, the cooperative effects generally associated with multiphosphorylation networks, and stresses the role of phosphatases in transforming graded phosphorylation signals into almost switchlike responses. The results are discussed in light of experiments that probe the distribution of phospho-residues.