Nat. Commun. 2020 Nov 25;11(1):5975. doi: 10.1038/s41467-020-19783-w.
The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation
Kaushik Bhattacharya 1, Lorenz Weidenauer 2, Tania Morán Luengo 3 4, Ellis C Pieters 3 4, Pablo C Echeverría 1 5, Lilia Bernasconi 1, Diana Wider 1, Yashar Sadian 6, Margreet B Koopman 3 4, Matthieu Villemin 1, Christoph Bauer 6, Stefan G D Rüdiger 3 4, Manfredo Quadroni 2, Didier Picard 7
Free article
Abstract
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.
- PMID: 33239621
- DOI: 10.1038/s41467-020-19783-w