Three J‑proteins impact Hsp104‑mediated variant‑specifc prion elimination: A new critical role for a low‑complexity domain

Prions are self-propagating protein isoforms that are typically amyloid. In Saccharomyces cerevisiae, amyloid prion aggregates are fragmented by a trio involving three classes of chaperone proteins: Hsp40s, also known as J-proteins, Hsp70s, and Hsp104. Hsp104, the sole Hsp100-class disaggregase in yeast, along with the Hsp70 Ssa and the J-protein Sis1, is required for the propagation of all known amyloid yeast prions. However, when Hsp104 is ectopically overexpressed, only the prion [PSI+] is efficiently eliminated from cell populations via a highly debated mechanism that also requires Sis1. Recently, we reported roles for two additional J-proteins, Apj1 and Ydj1, in this process. Deletion of Apj1, a J-protein involved in the degradation of sumoylated proteins, partially blocks Hsp104-mediated [PSI+] elimination. Apj1 and Sis1 were found to have overlapping functions, as overexpression of one compensates for loss of function of the other. In addition, overexpression of Ydj1, the most abundant J-protein in the yeast cytosol, completely blocks Hsp104-mediated curing. Yeast prions exhibit structural polymorphisms known as “variants”; most intriguingly, these J-protein effects were only observed for strong variants, suggesting variant-specific mechanisms. Here, we review these results and present new data resolving the domains of Apj1 responsible, specifically implicating the involvement of Apj1’s Q/S-rich low-complexity domain.

Title	Three J‑proteins impact Hsp104‑mediated variant‑specifc prion elimination: A new critical role for a low‑complexity domain
Creator	Kamiya, E.
	Nolte, A. N.
	Berger, S. E.
	Hines, Justin K.
Publisher	Current Genetics
Academic Department	Chemistry
Division	Natural Sciences
Organization	Lafayette College
Date Issued	2020
Date Available	2020-02-17
Type	Article
Language	English
Keyword	protein misfolding
	prion
	Hsp104
	yeast
	molecular chaperone
Bibliographic Citation	Berger, S. E., et al. (2020) "Three J‑proteins impact Hsp104‑mediated variant‑specifc prion elimination: A new critical role for a low‑complexity domain." Current Genetics 66.1 (2020): 51-8.
Standard Identifier	Handle 10385/wh246s54s
Standard Identifier	DOI 10.1007/s00294-019-01006-5
Permalink	http://hdl.handle.net/10385/wh246s54s
Rights Statement	Creative Commons - Attribution
Rights Holders	Kamiya, E.
	Nolte, A. N.
	Berger, S. E.
	Hines, Justin K.