Insights into the structure and dynamics of unfolded proteins from nuclear magnetic resonance

Abstract

Nuclear magnetic resonance (NMR) is unique in being able to provide detailed insights into the conformation of unfolded and partly folded proteins. This chapter presents the structure and dynamics of unfolded states, that is, equilibrium NMR studies of apomyoglobin; characterization of proteins that are unstructured under nondenaturing conditions; and intrinsically unstructured proteins (coupled folding and binding events). NMR is the method of choice to determine the conformational preferences inherent in these domains. NMR is also of the greatest utility in the elucidation of pathways of protein folding by allowing structural characterization of equilibrium and kinetic folding intermediates. Through the application of state-of-the-art heteronuclear NMR methods, new insights have been obtained into the nature of the conformational ensemble and the dynamics of denatured proteins. These studies show that the behavior of denatured proteins is typically far from that of a statistical random coil. This new view of the denatured state provides a basis for understanding the earliest events that occur during protein folding.