Phosphorylation‐Based Molecular Switches

Biochemical and structural exploration of how phosphorylation affects protein function will help the biological interpretation of large-scale phospho-proteomics and interactomics data, since phosphorylation affects macromolecular interactions, particularly protein–protein binding. The results of bottom–up and top–down strategies could come together through the elucidation of phospho-switches: short disordered protein regions functionally affected – for example, in their capacity to bind other proteins – by protein phosphorylation. This chapter explores the mechanisms through which protein phosphorylation affects protein function, discusses experimental and computational strategies in the exploration of phosphorylation-based molecular switches, and shows examples for phospho-switch-based regulation of biological processes.