Structural Disorder in Chaperone Functions Probed by NMR

Abstract

Molecular chaperones are essential for maintaining protein homeostasis in cells as they bind to unfolded polypeptides of client proteins and prevent them from misfolding. The solution NMR method has unique advantages in investigating chaperone–client interactions, particularly for special cases in which the chaperone itself requires partial or overall unfolding to gain functional activity. In this chapter, we summarize recent advances in understanding the functional mechanisms of these extremely dynamic and heterogeneous systems, including the stress-related conditional disordered chaperones Hsp33 and HdeA, small heat shock proteins and the linker histone chaperone prothymosin-α, with special focus on the application of a variety of NMR techniques to overcome the unique challenges in each case.