Development of new strategies to investigate intrinsically disordered proteins and their interactions

The interest in Intrinsically Disordered Proteins (IDPs) and Intrinsically Disordered Regions (IDRs) of complex proteins arises from the very different processes they can modulate in cells and viruses. These highly flexible molecules are biological tools that can be handled for different aims ranging from cell fate control to regulation of metabolism. For these reasons, their study covers different fields of research, from chemistry to medicine. Nuclear Magnetic Resonance (NMR) spectroscopy plays a central role in the characterization of IDPs/IDRs being a unique method able to provide atomic information on their structural and dynamic features. The peculiar properties of IDPs strongly influence the NMR observables thus improved experimental methods are needed in order to study these proteins and their interactions, especially when approaching physiological conditions. It is thus important to develop novel experiments optimized for the properties of IDPs and overcome the experimental limitations linked to their biochemical and biophysical properties. In this framework, 13C- detected experiments and high-field instrumentation provide a unique strategy to investigate IDPs/IDRs at atomic resolution in different experimental conditions and to disentangle the information on the heterogeneous nature of complex multi-domain proteins while mimicking the physiological milieu.