Structural analysis of proline-rich motifs in disordered protein

Proline-rich motifs (PRMs) and oligoproline stretches are abundant within intrinsically disordered proteins (IDPs). They are key to protein-protein interactions involved in biological processes such as cell signaling or neurodegenerative diseases. Despite their significance, the structural and dynamical behavior of PRMs is still poorly understood. Although NMR is a principal technique to provide detailed atom-resolved information on IDPs, for PRMs its use is strongly impaired by severe spectral overlap caused by the low chemical shift dispersion common in IDPs and the unique features of proline, such as the cis/trans peptide bond isomerization. We aim to develop new approaches to make the study of PRMs and oligoprolines possible at an unprecedented level of detail, based on pure shift methods and the introduction of fluorinated prolines. We aim to apply these methods on PRM systems involved in hormone-regulated gene expression, and Huntington's disease.