Hsp70 and Hsp110 Chaperones Promote Early Steps of Proteasome Assembly

• Published in: Biomolecules (Basel, Switzerland) Vol. 13; no. 1; p. 11
• Main Authors: Matias, Ana C, Matos, Joao, Dohmen, R Jürgen, Ramos, Paula C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.12.2022; MDPI
• Subjects: Biosynthesis; Chaperones; Core particles; Gene deletion; Genes; Hsp110; Hsp70; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Hsp70 protein; Humans; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Plasmids; Prokaryotes; proteasome biogenesis; Proteasome Endopeptidase Complex - metabolism; Proteasomes; Proteins; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Ssa1; Sse1; Ubiquitin; Yeast; Germany; Hsp70; Sse1; proteasome biogenesis; chaperones; Hsp110; Ssa1
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom13010011

Whereas assembly of the 20S proteasome core particle (CP) in prokaryotes apparently occurs spontaneously, the efficiency of this process in eukaryotes relies on the dedicated assembly chaperones Ump1, Pba1-Pba2, and Pba3-Pba4. For mammals, it was reported that CP assembly initiates with formation of a complete α-ring that functions as a template for β subunit incorporation. By contrast, we were not able to detect a ring composed only of a complete set of α subunits in Instead, we found that the CP subunits α1, α2, and α4 each form independent small complexes. Purification of such complexes containing α4 revealed the presence of chaperones of the Hsp70/Ssa and Hsp110/Sse families. Consistently, certain small complexes containing α1, α2, and α4 were not formed in strains lacking these chaperones. Deletion of the gene in combination with deletions of (α3), , or genes resulted in severe synthetic growth defects, high levels of ubiquitin-conjugates, and an accumulation of distinct small complexes with α subunits. Our study shows that Hsp70 and Hsp110 chaperones cooperate to promote the folding of individual α subunits and/or their assembly with other CP subunits, Ump1, and Pba1-Pba4 in subsequent steps.