NMR illuminates intrinsic disorder

Nuclear magnetic resonance (NMR) has long been instru-mental in the characterization of intrinsically disordered pro-teins (IDPs) and intrinsically disordered regions (IDRs). This method continues to offer rich insights into the nature of IDPs in solution, especially in combination with other biophysical methods such as small-angle scattering, single-molecule fluorescence, electron paramagnetic resonance (EPR), and mass spectrometry. Substantial advances have been made in recent years in studies of proteins containing both ordered and disordered domains and in the characterization of problematic sequences containing repeated tracts of a single or a few amino acids. These sequences are relevant to disease states such as Alzheimer's, Parkinson's, and Huntington's diseases, where disordered proteins misfold into harmful amyloid. Inno-vative applications of NMR are providing novel insights into mechanisms of protein aggregation and the complexity of IDP interactions with their targets. As a basis for understanding the solution structural ensembles, dynamic behavior, and func-tional mechanisms of IDPs and IDRs, NMR continues to prove invaluable.

Automated summary

Nuclear magnetic resonance (NMR) has been crucial in the study of intrinsically disordered proteins (IDPs) and regions (IDRs), providing valuable insights when combined with other biophysical methods. Recent advancements have been made in studying proteins with both ordered and disordered domains, as well as problematic sequences with repeated amino acid tracts. Innovative applications of NMR have offered new insights into protein aggregation mechanisms and interactions of disordered proteins with their targets. NMR remains invaluable in understanding the structural ensembles, dynamic behavior, and functional mechanisms of IDPs and IDRs.