The ER has many complex proteins and so have a robust system for heat-shock protein assisted folding

Small heat shock proteins (sHSPs) are a class of molecular chaperones that help maintain cellular proteostasis. Additionally, we examine the effects of disease-associated NTR mutations on HSPB1 structure and dynamics, leveraging our emerging structural insights. Phosphorylation-dependent interactions inform a mechanism by which HSPB1 is activated under stress conditions. The results support a model in which multiple grooves on the ACD interact with specific NTR regions, creating an ensemble of ‘quasi-ordered’ NTR states that can give rise to the known heterogeneity and plasticity of HSPB1. Here, we present a hybrid approach involving NMR, hydrogen-deuterium exchange mass spectrometry, and modeling to provide the first residue-level characterization of the NTR. In the human sHSP HSPB1, the disordered N-terminal region (NTR) represents nearly 50% of the sequence. Little is known about sHSP structure beyond its structured α-crystallin domain (ACD), which is flanked by disordered regions. Small heat shock proteins (sHSPs) are nature’s ‘first responders’ to cellular stress, interacting with affected proteins to prevent their aggregation.

The ER has many complex proteins and so have a robust system for heat-shock protein assisted folding