[PSI+] Maintenance Is Dependent on the Composition, Not Primary Sequence, of the Oligopeptide Repeat Domain

Toombs, James A.; Liss, Nathan M.; Cobble, Kacy R.; Ben-Musa, Zobaida; Ross, Eric D.

doi:10.1371/journal.pone.0021953

Cited by 34 publications

(36 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was proposed that the Sup35 (as well as New1) PrD can be divided into "aggregation" (QN stretch) and "propagation" (ORs) elements (Chernoff 2004a;Osherovich et al 2004) and that the propagation element is involved in interaction with Hsp104 (see Requirements for Prion Propagation: Shearing and Segregation). OR expansion increases de novo [PSI + ] generation (Liu and Lindquist 1999) although Ure2 or "scrambled" Sup35 PrDs lack ORs, indicating that ORs are not necessary for interaction with the chaperones responsible for prion propagation (Ross et al 2005b;Toombs et al 2011). Perhaps ORs are frequently associated with prions because the duplication events that generate them also extend the size of the regions with the amino acid compositions conducive to prion formation.…”

Section: Prion Domainsmentioning

confidence: 99%

Prions in Yeast

2012

View full text Add to dashboard Cite

The concept of a prion as an infectious self-propagating protein isoform was initially proposed to explain certain mammalian diseases. It is now clear that yeast also has heritable elements transmitted via protein. Indeed, the "protein only" model of prion transmission was first proven using a yeast prion. Typically, known prions are ordered cross-b aggregates (amyloids). Recently, there has been an explosion in the number of recognized prions in yeast. Yeast continues to lead the way in understanding cellular control of prion propagation, prion structure, mechanisms of de novo prion formation, specificity of prion transmission, and the biological roles of prions. This review summarizes what has been learned from yeast prions.

show abstract

Section: Prion Domainsmentioning

confidence: 99%

Prions in Yeast

2012

View full text Add to dashboard Cite

show abstract

“…We previously proposed a second mechanism for how yeast PFDs could rapidly evolve (23). Oligopeptide repeat segments are found in multiple prion proteins, including PrP, Sup35, and Rnq1, and expansion of the PrP (24) or Sup35 (25) repeats increases prion activity.…”

mentioning

confidence: 99%

“…If prion activity is insensitive to the primary sequence of the repeats, then why are repeats so common in PFDs? We proposed that oligopeptide repeats may be common in PFDs simply because they provide a simple genetic mechanism for generating PFDs (23). Tandem repeats, both of single codons and larger oligopeptide segments, are common in eukaryotic genomes and can readily form due to errors in replication, repair, or recombination (27,28).…”

mentioning

confidence: 99%

Generating new prions by targeted mutation or segment duplication

Paul

Hendrich

Waechter

et al. 2015

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

Self Cite

View full text Add to dashboard Cite

Yeasts contain various protein-based genetic elements, termed prions, that result from the structural conversion of proteins into self-propagating amyloid forms. Most yeast prion proteins contain glutamine/asparagine (Q/N)-rich prion domains that drive prion activity. Here, we explore two mechanisms by which new prion domains could evolve. First, it has been proposed that mutation and natural selection will tend to result in proteins with aggregation propensities just low enough to function under physiological conditions and thus that a small number of mutations are often sufficient to cause aggregation. We hypothesized that if the ability to form prion aggregates was a sufficiently generic feature of Q/N-rich domains, many nonprion Q/N-rich domains might similarly have aggregation propensities on the edge of prion formation. Indeed, we tested four yeast Q/N-rich domains that had no detectable aggregation activity; in each case, a small number of rationally designed mutations were sufficient to cause the proteins to aggregate and, for two of the domains, to create prion activity. Second, oligopeptide repeats are found in multiple prion proteins, and expansion of these repeats increases prion activity. However, it is unclear whether the effects of repeat expansion are unique to these specific sequences or are a generic result of adding additional aggregation-prone segments into a protein domain. We found that within nonprion Q/N-rich domains, repeating aggregation-prone segments in tandem was sufficient to create prion activity. Duplication of DNA elements is a common source of genetic variation and may provide a simple mechanism to rapidly evolve prion activity.

show abstract

“…While the GQ-rich region does not create a transmission barrier when deleted, it does contribute to prion formation through interactions with glutamine-asparagine-rich regions (Kadnar et al 2010). The repeat region of Sup35p is important for prion formation (Liu and Lindquist 1999;Parham et al 2001;Osherovich et al 2004), not because of the repeat feature, but because of the amino acid composition (Ross et al 2004;Ross et al 2005;Toombs et al 2011). The importance of repeats-as repeats-has not been tested for Rnq1p.…”

Section: Risk Factors For [Pin+] Infectionmentioning

confidence: 99%

Effect of Domestication on the Spread of the [PIN+] Prion inSaccharomyces cerevisiae

2014

View full text Add to dashboard Cite

Prions (infectious proteins) cause fatal neurodegenerative diseases in mammals. In the yeast Saccharomyces cerevisiae, many toxic and lethal variants of the [PSI+] and [URE3] prions have been identified in laboratory strains, although some commonly studied variants do not seem to impair cell growth. Phylogenetic analysis has revealed four major clades of S. cerevisiae that share histories of two prion proteins and largely correspond to different ecological niches of yeast. The [PIN+] prion was most prevalent in commercialized niches, infrequent among wine/vineyard strains, and not observed in ancestral isolates. As previously reported, the [PSI+] and [URE3] prions are not found in any of these strains. Patterns of heterozygosity revealed genetic mosaicism and indicated extensive outcrossing among divergent strains in commercialized environments. In contrast, ancestral isolates were all homozygous and wine/vineyard strains were closely related to each other and largely homozygous. Cellular growth patterns were highly variable within and among clades, although ancestral isolates were the most efficient sporulators and domesticated strains showed greater tendencies for flocculation.[PIN+]-infected strains had a significantly higher likelihood of polyploidy, showed a higher propensity for flocculation compared to uninfected strains, and had higher sporulation efficiencies compared to domesticated, uninfected strains. Extensive phenotypic variability among strains from different environments suggests that S. cerevisiae is a niche generalist and that most wild strains are able to switch from asexual to sexual and from unicellular to multicellular growth in response to environmental conditions. Our data suggest that outbreeding and multicellular growth patterns adapted for domesticated environments are ecological risk factors for the [PIN+] prion in wild yeast. P RIONS cause a variety of transmissible spongiform encephalopathies (TSEs) in mammals, including scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in cervids, and CreutzfeldtJakob disease (CJD) in humans. With all TSEs, endogenous prion protein (PrP) misfolds into an altered, usually proteaseresistant, isoform, termed "PrP res " (" res" for protease resistant). Several prions have been described in fungi (Wickner 1994), with many prion variants of the [PSI+] and [URE3] prions showing toxic or even lethal effects in Saccharomyces cerevisiae (McGlinchey et al. 2011). The [PSI+] prion of S. cerevisiae is formed from the cytosolic protein Sup35p. There are three distinct regions of Sup35p: a glutamine/ asparagine-rich N-terminal domain (amino acids 1-123) that is necessary and sufficient for prion formation (TerAvanesyan et al. 1994) and that facilitates deadenylation and decay of messenger RNA (Hosoda et al. 2003); a middle M domain (amino acids 124-253) of unknown function; and an essential C-terminal domain that functions during translation termination (reviewed by Wickner et al. 2004 (Derkatch et ...

show abstract

[PSI+] Maintenance Is Dependent on the Composition, Not Primary Sequence, of the Oligopeptide Repeat Domain

Cited by 34 publications

References 55 publications

Prions in Yeast

Prions in Yeast

Generating new prions by targeted mutation or segment duplication

Effect of Domestication on the Spread of the [PIN+] Prion inSaccharomyces cerevisiae

Contact Info

Product

Resources

About