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

Sharma, Deepak; Masison, Daniel C.

doi:10.1534/genetics.108.089458

Cited by 71 publications

(87 citation statements)

References 50 publications

(47 reference statements)

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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%

“…Growth of strain 1161, which lacks all four chromosomal SSA family genes (SSA1-SSA4), is supported equally well by Ssa1p or Ssa2p expressed from a plasmid (17), indicating that all essential Hsp70 functions of Ssa1p and Ssa2p are completely interchangeable. However, whereas [URE3] propagates stably in cells expressing only Ssa2p, it is unstable in cells expressing only Ssa1p (17).…”

Section: Resultsmentioning

confidence: 99%

“…However, whereas [URE3] propagates stably in cells expressing only Ssa2p, it is unstable in cells expressing only Ssa1p (17). This instability is seen as the appearance of red [ureo] colonies arising among a population of cells spread on a plate with limiting adenine (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Strain 1075 is MATa, kar1-1, SUQ5, P DAL5 ::ADE2, his3Δ202, leu2Δ1, trp1Δ63, ura3-52 (17). Strain 1161 has in addition ssa1:: KanMX, ssa2::HIS3, ssa3::TRP1, ssa4::ura3-2f and carries plasmid pJ401 (see below).…”

Section: Methodsmentioning

confidence: 99%

“…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).…”

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confidence: 99%

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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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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

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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Modulation of Amyloid Propagation in Yeast by Hsp70 and its Regulators and Chaperone Partners

Masison

2011

Protein Chaperones and Protection From Neurodegenerative Diseases

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Global gene expression analysis of Saccharomyces cerevisiae grown under redox potential‐controlled very‐high‐gravity conditions

Liu

Lin

Bai

2013

Biotechnology Journal

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Redox potential (ORP) plays a pivotal role in yeast viability and ethanol production during very-high-gravity (VHG) ethanol fermentation. In order to identify the correlation between redox potential profiles and gene expression patterns, global gene expression of Saccharomyces cerevisiae was investigated. Results indicated that significant changes in gene expression occurred at the periods of 0 - 6 h and 30 - 36 h, respectively. Changes noted in the period of 0 - 6 h were mainly related to carbohydrate metabolism. In contrast, gene expression variation at 30 - 36 h could be attributed primarily to stress response. Although CDC19 was down-regulated, expression of PYK2, PDC6 and ADH2 correlated inversely with ORP. Meanwhile, expression of GPD1 decreased due to the depletion of dissolved oxygen in the fermentation broth, but expression of GPD2 correlated with ORP. Transcription of genes encoding heat shock proteins was characterized by uphill, downhill, valley and plateau expression profiles, accordingly to specific function in stress response. These results highlight the role of ORP in modulating yeast physiology and metabolism under VHG conditions.

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

Cited by 71 publications

References 50 publications

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

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

Modulation of Amyloid Propagation in Yeast by Hsp70 and its Regulators and Chaperone Partners

Global gene expression analysis of Saccharomyces cerevisiae grown under redox potential‐controlled very‐high‐gravity conditions

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