Solution NMR Spectroscopy Provides an Avenue for the Study of Functionally Dynamic Molecular Machines: The Example of Protein Disaggregation

Solution-based NMR spectroscopy has been an important tool for studying the structure and dynamics of relatively small proteins and protein complexes with aggregate molecular masses under approximately 50 kDa. The development of new experiments and labeling schemes, coupled with continued improvements in hardware, has significantly reduced this size limitation, enabling atomic-resolution studies of molecular machines in the 1 MDa range. In this Perspective, some of the important advances are highlighted in the context of studies of molecular chaperones involved in protein disaggregation. New insights into the structural biology of disaggregation obtained from NMR studies are described, focusing on the unique capabilities of the methodology for obtaining atomic-resolution descriptions of dynamic systems.