The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation.

Hop/Stip1/Sti1 is thought to be essential as a co-chaperone to facilitate substrate transfer between the Hsp70 and Hsp90 molecular chaperones. Despite this proposed key function for protein folding and maturation, it is not essential in a number of eukaryotes and bacteria lack an ortholog. We set out to identify and ...
to characterize its eukaryote-specific function. Human cell lines and the budding yeast with deletions of the Hop/Sti1 gene display reduced proteasome activity due to inefficient capping of the core particle with regulatory particles. Unexpectedly, knock-out cells are more proficient at preventing protein aggregation and at promoting protein refolding. Without the restraint by Hop, a more efficient folding activity of the prokaryote-like Hsp70-Hsp90 complex, which can also be demonstrated in vitro, compensates for the proteasomal defect and ensures the proteostatic equilibrium. Thus, cells may act on the level and/or activity of Hop to shift the proteostatic balance between folding and degradation.
Mesh Terms:
A549 Cells, Gene Knockout Techniques, HCT116 Cells, HEK293 Cells, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, Heat-Shock Proteins, Humans, Mutagenesis, Site-Directed, Mutation, Proteasome Endopeptidase Complex, Protein Aggregates, Protein Folding, Proteolysis, Saccharomyces cerevisiae Proteins
Nat Commun
Date: Nov. 25, 2020
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