9NVK

mjHSP16.5 36mer (+lysozyme, 75C)

Summary for 9NVK

• Entry DOI: 10.2210/pdb9nvk/pdb
• EMDB information: 49838
• Descriptor: Small heat shock protein HSP16.5 (1 entity in total)
• Functional Keywords: shsp, thermophile, holdase, chaperone
• Biological source: Methanocaldococcus jannaschii
• Total number of polymer chains: 36
• Total formula weight: 592919.64

Authors

Miller, A.P.,Reichow, S.L. (deposition date: 2025-03-20, release date: 2025-04-16, Last modification date: 2025-05-07)

Primary citation

Miller, A.P.,Reichow, S.L.
Mechanism of small heat shock protein client sequestration and induced polydispersity.
Nat Commun, 16:3635-3635, 2025

PubMed Abstract: Small heat shock proteins (sHSPs) act as first responders during cellular stress, sequestering destabilized proteins (clients) to prevent aggregation and facilitate refolding or degradation. This critical function, conserved across all life, is linked to proteostasis and protein misfolding diseases. However, the extreme molecular plasticity of sHSP/client complexes has limited mechanistic understanding. Here, we present high-resolution cryo-EM structures of Methanocaldococcus jannaschii sHSP (mjHSP16.5) in apo and multiple client-bound states. The ensemble reveals molecular mechanisms of client sequestration, highlighting cooperative chaperone-client interactions. Client engagement polarizes scaffold stability, promoting higher-order assembly and enhanced sequestration. Higher-order states suggest multiple sHSP/client assembly pathways, including subunit insertion at destabilized geometrical features. These findings provide critical insights into sHSP chaperone function and the interplay between polydispersity and client handling under stress.

PubMed: 40240363
DOI: 10.1038/s41467-025-58964-3

Experimental method

ELECTRON MICROSCOPY (4.2 Å)