Mechanism of small heat shock protein client sequestration and induced polydispersity.

ABSTRACT: Small heat shock proteins (sHSPs) act as first responders during cellular stress by recognizing and sequestering destabilized proteins (clients), preventing their aggregation and facilitating downstream refolding or degradation^1-3. This chaperone function is critically important to proteostasis, conserved across all kingdoms of life, and associated with various protein misfolding diseases in humans^4,5. Mechanistic insights into how sHSPs sequester destabilized clients have been limited due to the extreme molecular plasticity and client-induced polydispersity of sHSP/client complexes^6-8. Here, we present high-resolution cryo-EM structures of the sHSP from Methanocaldococcus jannaschii (mjHSP16.5) in both the apo-state and in an ensemble of clie

SUBMITTER: Miller AP 

PROVIDER: S-EPMC11642849 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature