In recent years many examples of intrinsically disordered proteins (IDPs) appeared in the literature showing how their structural plasticity and intrinsic flexibility enable them to play key roles in many regulatory processes. Their mis-function has also been related to several diseases. The general properties of IDPs cannot be captured in ordered crystals, preventing them to be suitable targets for crystallographic studies. Thus, nuclear magnetic resonance (NMR) spectroscopy plays a crucial role in their investigation, being the only method that allows a high resolution description of their structural and dynamic features in solution.
IDPs are often enriched in the so-called disorder promoting amino acids, among which proline residues have a particular prominence. Proline residues have peculiar physicochemical properties and generally they are not mapped with NMR experiments based on amide-proton detection. Notwithstanding, their role in globular proteins has been studied in detail since decades revealing interesting functional roles. On the contrary, despite their high abundance and presence in many peculiar motifs characteristic of IDPs, the role of proline residues in protein disorder has not yet been addressed in detail.
Examples of proline-rich IDPs will give us the opportunity to discuss the different roles played by proline residues depending on their sequence context.