The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation
| Autor: | Bhattacharya, Kaushik, Weidenauer, Lorenz, Luengo, Tania Morán, Pieters, Ellis C., Echeverría, Pablo C., Bernasconi, Lilia, Wider, Diana, Sadian, Yashar, Koopman, Margreet B., Villemin, Matthieu, Bauer, Christoph, Rüdiger, Stefan G. D., Quadroni, Manfredo, Picard, Didier |
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| Přispěvatelé: | Echeverría, Pablo C [0000-0003-1367-9692], Rüdiger, Stefan GD [0000-0002-1807-2972], Quadroni, Manfredo [0000-0002-2720-4084], Picard, Didier [0000-0001-8816-9668], Apollo - University of Cambridge Repository, Sub Cellular Protein Chemistry, Cellular Protein Chemistry |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Proteasome Endopeptidase Complex
Protein Folding Saccharomyces cerevisiae Proteins Chemistry(all) Science Physics and Astronomy(all) Article Gene Knockout Techniques Protein Aggregates ddc:590 ddc:570 Chaperones Humans HSP70 Heat-Shock Proteins HSP90 Heat-Shock Proteins Heat-Shock Proteins Proteasome Mass spectrometry Biochemistry Genetics and Molecular Biology(all) HCT116 Cells Protein quality control HEK293 Cells A549 Cells Mutation Proteolysis Mutagenesis Site-Directed |
| Zdroj: | Nature communications, vol. 11, no. 1, pp. 5975 Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-21 (2020) Nature Communications, Vol. 11, No 5975 (2020) |
| ISSN: | 2041-1723 |
| Popis: | 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. Hop, also known as Stip1 or Sti1, facilitates substrate transfer between the Hsp70 and Hsp90 molecular chaperones. Characterization of proteostasis-related pathways in STIP1 knock-out cell lines reveals that in eukaryotes Stip1 modulates the balance between protein folding and degradation. |
| Databáze: | OpenAIRE |
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