Amyloid-associated activity contributes to the severity and toxicity of a prion phenotype

John A. Pezza, Janice Villali, Suzanne S. Sindi, Tricia R Serio

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The self-assembly of alternative conformations of normal proteins into amyloid aggregates has been implicated in both the acquisition of new functions and in the appearance and progression of disease. However, while these amyloidogenic pathways are linked to the emergence of new phenotypes, numerous studies have uncoupled the accumulation of aggregates from their biological consequences, revealing currently underappreciated complexity in the determination of these traits. Here, to explore the molecular basis of protein-only phenotypes, we focused on the Saccharomyces cerevisiae Sup35/[PSI + ] prion, which confers a translation termination defect and expression level-dependent toxicity in its amyloid form. Our studies reveal that aggregated Sup35 retains its normal function as a translation release factor. However, fluctuations in the composition and size of these complexes specifically alter the level of this aggregate-associated activity and thereby the severity and toxicity of the amyloid state. Thus, amyloid heterogeneity is a crucial contributor to protein-only phenotypes.

Original languageEnglish (US)
Article number4384
JournalNature Communications
Volume5
DOIs
StatePublished - Jul 15 2014

Fingerprint

phenotype
Prions
Amyloid
toxicity
Toxicity
proteins
Phenotype
Amyloidogenic Proteins
saccharomyces
Protein Conformation
progressions
Yeast
Self assembly
Saccharomyces cerevisiae
Disease Progression
Conformations
self assembly
acquisition
Proteins
Defects

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Amyloid-associated activity contributes to the severity and toxicity of a prion phenotype. / Pezza, John A.; Villali, Janice; Sindi, Suzanne S.; Serio, Tricia R.

In: Nature Communications, Vol. 5, 4384, 15.07.2014.

Research output: Contribution to journalArticle

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