Simulating Mono-and Multi-Protein Phosphorylation within Nanoclusters

TL;DR

This paper presents a theoretical simulation of how proteins undergo mono- and multi-phosphorylation within nanoclusters, revealing complex regulation mechanisms and the influence of biophysical parameters on phosphorylation states.

Contribution

It introduces a novel simulation approach that models the interplay between mono- and multi-phosphorylation in nanoclusters, emphasizing the role of phosphatases and cooperative effects.

Findings

Phosphorylation states depend on diffusion and dwell time parameters.

Multi-phosphorylation exhibits cooperative effects influencing cluster behavior.

Phosphatases can switch phosphorylation signals from graded to binary responses.

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 post-translational modifications, such as mono-and multi-phosphorylation and dephosphorylation of residues. We theoretically simulate how a protein can be either mono-or multi-phosphorylated 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 multi-phosphorylation, the cooperative effects generally associated with multi-phosphorylation networks, and stresses the role of phosphatases in transforming graded phosphorylation signals into almost switch-like responses. The results are discussed in light of experiments that probe the distribution of phospho-residues.