Solution NMR Studies of Chaperone–Client Systems

Abstract

Proper folding of many nascent polypeptides often requires assistance from a class of proteins called molecular chaperones, which bind to newly synthesized proteins and prevent misfolding or aggregation. Mechanistic understanding of this essential process, however, has been greatly hampered by the scarcity of structural knowledge on how chaperones recognize and interact with their client proteins. The main barrier lies in the inherently highly dynamic interaction nature that governs the promiscuous binding mechanism of chaperones to the flexible, unfolded or partially unfolded substrate proteins. By virtue of breakthroughs in tackling the molecular size limit and the advantages of dynamic tracking, solution nuclear magnetic resonance (NMR) spectroscopy has become one of the most powerful tools to study chaperone–client systems. Here we briefly summarize the recent advancements in solution NMR techniques that have been commonly applied in large proteins and present an overview of multiple contributions of this technique to chaperone–client systems.