Hsp40s Specify Functions of Hsp104 and Hsp90 Protein Chaperone Machines

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The cellular chaperone machinery helps proteins adopt and maintain native conformations and protects cells from stress. The yeast Hsp40s Ydj1 and Sis1 are co-chaperones that regulate Hsp70s, which are key components of many chaperone complexes. Both of these Hsp40s are crucial for growth and Ydj1 directs disaggregation activity of the Hsp100-based machinery to provide stress protection while Sis1 directs this activity to promote prion replication. Ydj1 also cures yeast of certain prions when overexpressed. We show that C-terminal domains that possess substrate-binding function of Ydj1 and Sis1 can mediate these and other functional distinctions and that the degree that prions depend on Sis1 activities could underlie differences in how they respond to alterations of chaperones. These findings support a view that Hsp40s regulate and specify functions of the chaperone machinery through substrate discrimination and cooperation with Hsp70. The disproportionate evolutionary expansion of Hsp40s (J-proteins) relative to their Hsp70 partners led to a proposal that this amplification allows increased regulation and fine-tuning of chaperone machines for increasingly complex processes. Our findings support this idea and provide insight into fundamental aspects of this cooperation.

Vyšlo v časopise: Hsp40s Specify Functions of Hsp104 and Hsp90 Protein Chaperone Machines. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004720
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004720

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