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bioRxiv · 10.1101/750646

Interplay of disordered and ordered regions of a human small heat shock protein yields an ensemble of \"quasi-ordered\" states.

Clouser, A. F.·Baughman, H. E.·Basanta, B.·Guttman, M.·Nath, A.·Klevit, R. E.
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Abstract

Small heat shock proteins (sHPSs) are natures \"first responders\" to cellular stress, interacting with affected proteins to prevent their aggregation. Little is known about sHSP structure beyond its structured -crystallin domain (ACD), which is flanked by disordered regions. In the human sHSP HSPB1, the disordered N-terminal region (NTR) represents nearly 50% of the sequence. 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. 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. Phosphorylation-dependent interactions inform a mechanism by which HSPB1 is activated under stress conditions. Additionally, we examine the effects of disease-associated NTR mutations on HSPB1 structure and dynamics, leveraging our emerging structural insights.

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Clouser, A. F., Baughman, H. E., Basanta, B., Guttman, M., Nath, A., Klevit, R. E.. 2019-08-29. Interplay of disordered and ordered regions of a human small heat shock protein yields an ensemble of \"quasi-ordered\" states.. https://doi.org/10.1101/750646

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