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Prion species barrier between the closely related yeast proteins is detected despite coaggregation.

ABSTRACT: Prions are self-perpetuating and, in most cases, aggregation-prone protein isoforms that transmit neurodegenerative diseases in mammals and control heritable traits in yeast. Prion conversion requires a very high level of identity of the interacting protein sequences. Decreased transmission of the prion state between divergent proteins is termed "species barrier" and was thought to occur because of the inability of divergent prion proteins to coaggregate. Species barrier can be overcome in cross-species infections, e.g., from "mad cows" to humans. We studied the counterparts of yeast prion protein Sup35, originated from three different species of the Saccharomyces sensu stricto group and exhibiting the range of prion domain divergence that overlaps with the range of divergence observed among distant mammalian species. All three proteins were capable of forming a prion in Saccharomyces cerevisiae, although prions formed by heterologous proteins were usually less stable than the endogenous S. cerevisiae prion. Heterologous Sup35 proteins coaggregated in the S. cerevisiae cells. However, in vivo cross-species prion conversion was decreased and in vitro polymerization was cross-inhibited in at least some heterologous combinations, thus demonstrating the existence of prion species barrier. Moreover, the barrier between the S. cerevisiae protein and its Saccharomyces paradoxus and Saccharomyces bayanus counterparts was asymmetric both in vivo and in vitro. Our data show that a decreased cross-species prion transmission does not necessarily correlate with a lack of cross-species coaggregation, suggesting that species-specificity of prion transmission is controlled at the level of conformational transition rather than coaggregation.

SUBMITTER: Chen B

PROVIDER: S-EPMC1815260 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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Prion species barrier between the closely related yeast proteins is detected despite coaggregation.

Chen Buxin B Newnam Gary P GP Chernoff Yury O YO

Proceedings of the National Academy of Sciences of the United States of America 20070212 8

Prions are self-perpetuating and, in most cases, aggregation-prone protein isoforms that transmit neurodegenerative diseases in mammals and control heritable traits in yeast. Prion conversion requires a very high level of identity of the interacting protein sequences. Decreased transmission of the prion state between divergent proteins is termed "species barrier" and was thought to occur because of the inability of divergent prion proteins to coaggregate. Species barrier can be overcome in cross ...[more]

PMID: 17296932

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Project description:BackgroundPrions are transmissible, propagating alternative states of proteins, and are usually made from the fibrillar, beta-sheet-rich assemblies termed amyloid. Prions in the budding yeast Saccharomyces cerevisiae propagate heritable phenotypes, uncover hidden genetic variation, function in large-scale gene regulation, and can act like diseases. Almost all these amyloid prions have asparagine/glutamine-rich (N/Q-rich) domains. Other proteins, that we term here 'prionogenic amyloid formers' (PAFs), have been shown to form amyloid in vivo, and to have N/Q-rich domains that can propagate heritable states in yeast cells. Also, there are >200 other S.cerevisiae proteins with prion-like N/Q-rich sequence composition. Furthermore, human proteins with such N/Q-rich composition have been linked to the pathomechanisms of neurodegenerative amyloid diseases.ResultsHere, we exploit the increasing abundance of complete fungal genomes to examine the ancestry of prions/PAFs and other N/Q-rich proteins across the fungal kingdom. We find distinct evolutionary behavior for Q-rich and N-rich prions/PAFs; those of ancient ancestry (outside the budding yeasts, Saccharomycetes) are Q-rich, whereas N-rich cases arose early in Saccharomycetes evolution. This emergence of N-rich prion/PAFs is linked to a large-scale emergence of N-rich proteins during Saccharomycetes evolution, with Saccharomycetes showing a distinctive trend for population sizes of prion-like proteins that sets them apart from all the other fungi. Conversely, some clades, e.g. Eurotiales, have much fewer N/Q-rich proteins, and in some cases likely lose them en masse, perhaps due to greater amyloid intolerance, although they contain relatively more non-N/Q-rich predicted prions. We find that recent mutational tendencies arising during Saccharomycetes evolution (i.e., increased numbers of N residues and a tendency to form more poly-N tracts), contributed to the expansion/development of the prion phenomenon. Variation in these mutational tendencies in Saccharomycetes is correlated with the population sizes of prion-like proteins, thus implying that selection pressures on N/Q-rich protein sequences against amyloidogenesis are not generally maintained in budding yeasts.ConclusionsThese results help to delineate further the limits and origins of N/Q-rich prions, and provide insight as a case study of the evolution of compositionally-defined protein domains.

Dataset Information

Prion species barrier between the closely related yeast proteins is detected despite coaggregation.

Publications

Prion species barrier between the closely related yeast proteins is detected despite coaggregation.

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