High-Resolution tools to target intrinsically disordered proteins

Nuclear Magnetic Resonance (NMR) is one of the most powerful techniques exploited in structural biology. While the NMR strategies for the study of folded proteins are well established, Intrinsically Disordered Proteins (IDPs) pose new challenges to the technique. Special precautions must be taken due to the lack of 3D structure and to the high flexibility provided by these macromolecules. In this frame 13C direct detection represents one of the best options to deal with the structural and dynamic features of IDPs. However, many steps forward have still to be taken to expand the NMR toolbox for the study of this class of biologically relevant proteins. In this doctoral thesis, my contribution to the advancement of NMR spectroscopy for the study of IDPs is described. Mainly, I’ve focused on the development and application of new NMR methods. The new strategies enable the characterization of dynamic processes, facilitate the acquisition of spectra with high content of information in a reduced time and allow the identification of new key motifs in IDPs. Moreover, the outcomes from the study of two biologically relevant viral proteins are presented. Through the proposed advances new motifs are identified in different IDPs, providing information of general interest and demonstrating the general applicability of these methods.