Prokaryotic Chaperones Support Yeast Prions and Thermotolerance and Define Disaggregation Machinery Interactions

Reidy, Michael; Miot, Marika; Masison, Daniel C.

doi:10.1534/genetics.112.142307

Cited by 57 publications

(89 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistently, ClpB, the bacterial homolog of Hsp104, cooperates with the bacterial Hsp70 system in protein disaggregation (8)(9)(10). Although it was presumed that ClpB could not remodel yeast prions (23), it was shown recently that ClpB could replace yeast Hsp104 in vivo when DnaK and GrpE are also present (24).…”

mentioning

confidence: 98%

Heat shock protein (Hsp) 70 is an activator of the Hsp104 motor

Lee¹,

Kim²,

Biter³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

104

111

View full text Add to dashboard Cite

Heat shock protein (Hsp) 104 is a ring-forming, protein-remodeling machine that harnesses the energy of ATP binding and hydrolysis to drive protein disaggregation. Although Hsp104 is an active ATPase, the recovery of functional protein requires the speciesspecific cooperation of the Hsp70 system. However, like Hsp104, Hsp70 is an active ATPase, which recognizes aggregated and aggregation-prone proteins, making it difficult to differentiate the mechanistic roles of Hsp104 and Hsp70 during protein disaggregation. Mapping the Hsp70-binding sites in yeast Hsp104 using peptide array technology and photo-cross-linking revealed a striking conservation of the primary Hsp70-binding motifs on the Hsp104 middle-domain across species, despite lack of sequence identity. Remarkably, inserting a Strep-Tactin binding motif at the spatially conserved Hsp70-binding site elicits the Hsp104 protein disaggregating activity that now depends on Strep-Tactin but no longer requires Hsp70/40. Consistent with a Strep-Tactin-dependent activation step, we found that full-length Hsp70 on its own could activate the Hsp104 hexamer by promoting intersubunit coordination, suggesting that Hsp70 is an activator of the Hsp104 motor.ClpB | DnaK | Hsp100 | molecular chaperone

show abstract

mentioning

confidence: 98%

Heat shock protein (Hsp) 70 is an activator of the Hsp104 motor

Lee¹,

Kim²,

Biter³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

104

111

View full text Add to dashboard Cite

show abstract

“…organisms (Reidy and Masison 2012;Reidy et al 2013). The prion domains of Ure2p and Sup35p form prions in vivo more readily than do the corresponding full-length proteins (Masison and Wickner 1995;Kochneva-Pervukhova et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Sporadic Distribution of Prion-Forming Ability of Sup35p from Yeasts and Fungi

et al. 2014

View full text Add to dashboard Cite

Sup35p of Saccharomyces cerevisiae can form the [PSI+] prion, an infectious amyloid in which the protein is largely inactive. The part of Sup35p that forms the amyloid is the region normally involved in control of mRNA turnover. The formation of [PSI+] by Sup35p's from other yeasts has been interpreted to imply that the prion-forming ability of Sup35p is conserved in evolution, and thus of survival/fitness/evolutionary value to these organisms. We surveyed a larger number of yeast and fungal species by the same criteria as used previously and find that the Sup35p from many species cannot form prions. [PSI+] could be formed by the Sup35p from Candida albicans, Candida maltosa, Debaromyces hansenii, and Kluyveromyces lactis, but orders of magnitude less often than the S. cerevisiae Sup35p converts to the prion form. The Sup35s from Schizosaccharomyces pombe and Ashbya gossypii clearly do not form [PSI+]. We were also unable to detect [PSI+] formation by the Sup35ps from Aspergillus nidulans, Aspergillus fumigatus, Magnaporthe grisea, Ustilago maydis, or Cryptococcus neoformans. Each of two C. albicans SUP35 alleles can form [PSI+], but transmission from one to the other is partially blocked. These results suggest that the prion-forming ability of Sup35p is not a conserved trait, but is an occasional deleterious side effect of a protein domain conserved for another function. P RIONS are infectious proteins, proteins that are altered in such a way that they can instruct the unaltered form of the same protein to undergo the same alteration. Vertical or horizontal transmission of the altered form to a new individual restarts the process of converting the unaltered form to the altered form. If the presence of the altered form has some toxic or other effect, or if the absence of the unaltered form is detectable, then a phenotype or disease is produced (reviewed in Liebman and Chernoff 2012;Wickner et al. 2013). Most prions are an amyloid form of a normally nonamyloid protein.Amyloid is a linear polymer of a single-protein species, composed largely of b-sheets, with the b-strands perpendicular to the long axis of the filaments.In yeast, as in other organisms, infection means horizontal transmission to a neighboring cell, not necessarily related to the cell that is the source of the infection. Perhaps because of yeast's tough cell wall, neither the RNA viruses of yeast nor yeast prions leave one cell to travel through the medium and enter another cell. Rather, they are passed from cell to cell by mating and were first found as nonchromosomal genetic elements. This horizontal spread (infection) is conveniently shown by cytoduction (cytoplasmic mixing), in which two cells mate, but do not fuse their nuclei, which separate in the subsequent cell division. However, the resulting daughter cells with the parental nuclei each have mixed cytoplasms. If one parent strain carried a prion and the other not, both daughter cells will be found to carry it. A self-propagating amyloid that is not passed from cell to cell by t...

show abstract

“…The collaboration of a yeast J-protein with the bacterial chaperones was demonstrated via a single point mutation in DnaK that was shown earlier to block interaction with Hsp40 [77]. Together with normal ClpB and GrpE, this mutant DnaK failed to function in yeast, indicating that a yeast J-protein was involved [60]. Finally, Reidy and colleagues took advantage of a known compensatory mutation in Hsp40's HPD motif that restored interaction with the defective DnaK [77].…”

Section: Generalized Role Of Sis1 In Prion Propagationmentioning

confidence: 98%

“…While Hsp104 plays a pivotal role in yeast prion propagation, Hsp104 does not work alone. In fact, under normal conditions Hsp100 disaggregases, such as Hsp104 and its Escherichia coli ortholog ClpB, are inactive without the cooperation of Hsp70 and the obligate Hsp70 cochaperone J-protein (also known as Hsp40), both in vivo and in vitro [60,61].…”

Section: Yeast Prion Biologymentioning

confidence: 99%

“…Finally, Reidy and colleagues took advantage of a known compensatory mutation in Hsp40's HPD motif that restored interaction with the defective DnaK [77]. They introduced this mutation into Sis1 or Ydj1, the two major yeast Hsp40s and after introduction into the system expressing ClpB, GrpE and the mutant DnaK, they discovered that, remarkably, Sis1 is the Hsp40 that the system collaborated with propagate prions, but the same system worked with Ydj1 in thermotolerance [60]. Thus, the Hsp40 component of the system specified the substrate type, with Sis1 required for amyloid substrates (prions) and Ydj1 required for heat-induced non-structured aggregates.…”

Section: Generalized Role Of Sis1 In Prion Propagationmentioning

confidence: 99%

See 1 more Smart Citation

The Role of the Hsp40 Chaperone Sis1 in Yeast Prion Propagation

Reidy¹

2017

Prion - An Overview

Self Cite

View full text Add to dashboard Cite

Yeast prions are self-templating amyloid aggregates composed of misfolded cellular proteins. In order to propagate, yeast prions must be broken into heritable seeds that are passed to subsequent generations. The replication step of the prion propagation cycle is accomplished by the actions of molecular chaperones, which bind to and serve the fibers through a process called disaggregation. Prions can be thought of as molecular diseases that have hijacked the chaperones for their continued existence. When viewed in this way, the study of yeast prions has been very informative about the interactions among of the molecular chaperones. This chapter focuses on the role of a single Hsp40 or J-protein, Sis1, in the propagation of yeast prions. While Sis1 seems to be required for the maintenance of many different prions, various prions depend on Sis1 in different ways, perhaps due to differences in underlying amyloid structure. New evidence is emerging that Sis1 is important for processes that may not involve prion replication activity, providing an intriguing alternative explanation for the observed differences in the prions' reliance on Sis1.

show abstract

Prokaryotic Chaperones Support Yeast Prions and Thermotolerance and Define Disaggregation Machinery Interactions

Cited by 57 publications

References 60 publications

Heat shock protein (Hsp) 70 is an activator of the Hsp104 motor

Heat shock protein (Hsp) 70 is an activator of the Hsp104 motor

Sporadic Distribution of Prion-Forming Ability of Sup35p from Yeasts and Fungi

The Role of the Hsp40 Chaperone Sis1 in Yeast Prion Propagation

Contact Info

Product

Resources

About