[URE3] prion propagation is abolished by a mutation of the primary cytosolic Hsp70 of budding yeast

Roberts, Bruce R.; Moriyama, Hiromitsu; Wickner, Reed B.

doi:10.1002/yea.1062

Cited by 62 publications

(55 citation statements)

References 49 publications

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“…In contrast, [URE3] propagation appears normal in ssa1D cells but unstable in ssa2D cells (Roberts et al 2004). We confirm these results ( Figure 1) and present a summary of how the different combinations of Ssa1p and Ssa2p affect prion propagation in Cells from white colonies on 1/2YPD were streaked or diluted in water and spread onto 1/2YPD plates and grown for 3 days at 30°followed by 5 days at 23°.…”

supporting

confidence: 83%

Functionally Redundant Isoforms of a Yeast Hsp70 Chaperone Subfamily Have Different Antiprion Effects

Sharma

Masison

2008

Genetics

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supporting

confidence: 83%

Functionally Redundant Isoforms of a Yeast Hsp70 Chaperone Subfamily Have Different Antiprion Effects

Sharma

Masison

2008

Genetics

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“…Previously, we and others showed that [URE3] propagation is inhibited by increasing Ssa1p or depleting Ssa2p, but not by increasing Ssa2p or depleting Ssa1p (16)(17)(18)(19). We assessed functions of purified Ssa1p and Ssa2p in vitro to determine whether these differences might be due to differences in their biochemical activities.…”

Section: Resultsmentioning

confidence: 97%

“…Prions are infectious amyloid-like aggregates of misfolded cellular proteins that propagate by inducing similar misfolding of the native form of protein. Yeast [URE3] prions, which propagate as amyloid forms of Ure2p, are unaffected by depletion of Ssa1p but are lost frequently from cells lacking Ssa2p (16,17). Also, increasing abundance of Ssa1p in wild-type cells causes them to lose [URE3], whereas increasing Ssa2p does not (18).…”

mentioning

confidence: 99%

Single methyl group determines prion propagation and protein degradation activities of yeast heat shock protein (Hsp)-70 chaperones Ssa1p and Ssa2p

Sharma

Masison²

2011

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

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Organisms encode multiple homologous heat shock protein (Hsp)-70s, which are essential protein chaperones that play the major role in cellular protein "quality control." Although Hsp70s are functionally redundant and highly homologous, many possess distinct functions. A regulatory motif underlying such distinctions, however, is unknown. The 98% identical cytoplasmic Hsp70s Ssa1p and Ssa2p function differently with regard to propagation of yeast [URE3] prions and in the vacuolar-mediated degradation of gluconeogenesis enzymes, such as FBPase. Here, we show that the Hsp70 nucleotide binding domain (NBD) regulates these functional specificities. We find little difference in ATPase, protein refolding, and amyloid inhibiting activities of purified Ssa1p and Ssa2p, but show that interchanging NBD residue alanine 83 (Ssa1p) and glycine 83 (Ssa2p) switched functions of Ssa1p and Ssa2p in [URE3] propagation and FBPase degradation. Disrupting the degradation pathway did not affect prion propagation, however, indicating these are two distinct processes where Ssa1/2p chaperones function differently. Our results suggest that the primary evolutionary pressure for Hsp70 functional distinctions is not to specify interactions of Hsp70 with substrate, but to specify the regulation of this activity. Our data suggest a rationale for maintaining multiple Hsp70s and suggest that subtle differences among Hsp70s evolved to provide functional specificity without affecting overall enzymatic activity.

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“…Overexpression of Ydj1-Hsp40 or Ssa1-Hsp70 (but not Ssa2-Hsp70) is able to cure [URE3] [78,89]. In addition, a missense mutation within the Ssa2-Hsp70 peptide-binding domain alters [URE3] stability [90]. Detailed genetic analysis has identified mutations in both the ATPase and peptide-binding domains of Ssa1-Hsp70 that alter stability of the [PSI + ] prion [91,92].…”

Section: Chaperonesmentioning

confidence: 99%

The yeast prion protein Ure2: Structure, function and folding

Lian

Jiang

Zhang

et al. 2006

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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The Saccharomyces cerevisiae protein Ure2 functions as a regulator of nitrogen metabolism and as a glutathione-dependent peroxidase. Ure2 also has the characteristics of a prion, in that it can undergo a heritable conformational change to an aggregated state; the prion form of Ure2 loses the regulatory function, but the enzymatic function appears to be maintained. A number of factors are found to affect the prion properties of Ure2, including mutation and expression levels of molecular chaperones, and the effect of these factors on structure and stability are being investigated. The relationship between structure, function and folding for the yeast prion Ure2 are discussed.

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[URE3] prion propagation is abolished by a mutation of the primary cytosolic Hsp70 of budding yeast

Abstract: Abstract

Cited by 62 publications

References 49 publications

Functionally Redundant Isoforms of a Yeast Hsp70 Chaperone Subfamily Have Different Antiprion Effects

Functionally Redundant Isoforms of a Yeast Hsp70 Chaperone Subfamily Have Different Antiprion Effects

Single methyl group determines prion propagation and protein degradation activities of yeast heat shock protein (Hsp)-70 chaperones Ssa1p and Ssa2p

The yeast prion protein Ure2: Structure, function and folding

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