Conformational Characterization of Intrinsically Disordered Proteins and Its Biological Significance

Abstract

Intrinsically disordered proteins (IDPs) perform a large variety of functions that are crucial for signaling, cell regulation, and homeostasis. Functions performed by IDPs are complementary to those executed by their globular counterparts demonstrating that the biophysical properties of disordered proteins dictate their functional mechanisms. Conformational plasticity, large solvent accessibility, and transient structuration are inherent characteristics of IDPs that are ideal to modulate partner recognition in signaling processes. As a consequence, the characterization of the structural features of IDPs in their free state and in complex with the relevant biological partners is crucial to reveal the molecular basis of signaling and cell regulation. Nuclear magnetic resonance (NMR) is the only structural biology technique to derive structural and dynamic information of IDPs at the residue level. NMR can probe the conformational landscape of IDPs and monitor the changes exerted by environmental conditions, posttranslational modifications, or recognition events. Through multiple parameters, NMR is a rich source of structural and dynamic information covering residue-specific conformational and long-range intramolecular interactions. Additionally, NMR data can be complemented by information obtained from other biophysical techniques such as small-angle X-ray scattering (SAXS) that probe the overall properties of the protein in solution. This chapter aims at describing the main technical and conceptual developments that have enabled NMR to decipher the structural basis of the biological role of IDPs in multitude of crucial biological processes.