Intrinsically disordered proteins: Methods for structure and dynamics studies

Intrinsically disordered proteins (IDPs) partially or completely lack a cooperatively folded structure under native conditions, preventing their equilibrium state from being adequately described by a single structural model. Reaching the goal of quantitatively describing IDP structure-function relationships has required the development of novel experiments aiming to characterize their structure and dynamics. This article will cover the state of the art in defining IDP structures, with particular emphasis on the role NMR has to play in resolving this grand challenge. In addition, the article will close with a survey of contemporary computational approaches to utilizing NMR structural constraints for IDP model generation. As a case study aiming to motivate the points made, examples will be provided from our investigation of the intrinsically disordered C-terminal region of FCP1 and its interaction with the cooperatively folded winged-helix domain from Rap74. Keywords: NMRresonance assignment, residual dipolar couplings, paramagnetic relaxation enhancement, spin relaxation, carbon detection, ensemble model, structure determination, molecular dynamics, IDP, FCP1