Hsp40s specify functions of Hsp104 and Hsp90 protein chaperone machines

• Published in: PLoS genetics Vol. 10; no. 10; p. e1004720
• Main Authors: Reidy, Michael, Sharma, Ruchika, Shastry, Shankar, Roberts, Brittany-Lee, Albino-Flores, Ivan, Wickner, Sue, Masison, Daniel C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.10.2014; Public Library of Science (PLoS)
• Subjects: Binding Sites; Biology and Life Sciences; Endopeptidase Clp; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Genetic aspects; Glutathione Peroxidase - genetics; Glutathione Peroxidase - metabolism; Heat shock proteins; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; HSP40 Heat-Shock Proteins - genetics; HSP40 Heat-Shock Proteins - metabolism; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; HSP90 Heat-Shock Proteins - metabolism; Machinery; Microorganisms; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Mutation; Peptide Termination Factors - genetics; Peptide Termination Factors - metabolism; Plasmids; Prions; Prions - genetics; Prions - metabolism; Protein Structure, Tertiary; Proteins; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Yeast; Yeast fungi
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1004720

Hsp100 family chaperones of microorganisms and plants cooperate with the Hsp70/Hsp40/NEF system to resolubilize and reactivate stress-denatured proteins. In yeast this machinery also promotes propagation of prions by fragmenting prion polymers. We previously showed the bacterial Hsp100 machinery cooperates with the yeast Hsp40 Ydj1 to support yeast thermotolerance and with the yeast Hsp40 Sis1 to propagate [PSI+] prions. Here we find these Hsp40s similarly directed specific activities of the yeast Hsp104-based machinery. By assessing the ability of Ydj1-Sis1 hybrid proteins to complement Ydj1 and Sis1 functions we show their C-terminal substrate-binding domains determined distinctions in these and other cellular functions of Ydj1 and Sis1. We find propagation of [URE3] prions was acutely sensitive to alterations in Sis1 activity, while that of [PIN+] prions was less sensitive than [URE3], but more sensitive than [PSI+]. These findings support the ideas that overexpressing Ydj1 cures [URE3] by competing with Sis1 for interaction with the Hsp104-based disaggregation machine, and that different prions rely differently on activity of this machinery, which can explain the various ways they respond to alterations in chaperone function.