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

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  • John A. Pezza

    (Brown University, Cell Biology and Biochemistry
    Present address: New England Biolabs, 240 County Road, Ipswich, Massachusetts, 01938, USA)

  • Janice Villali

    (Brown University, Cell Biology and Biochemistry
    Present address: Department of Biochemistry, Brandeis University, 415 South Street, Waltham, Massachusetts 02454, USA)

  • Suzanne S. Sindi

    (Merced Applied Mathematics, School of Natural Sciences, University of California)

  • Tricia R. Serio

    (Brown University, Cell Biology and Biochemistry
    Present address: Department of Molecular and Cellular Biology, The University of Arizona, 1007 E. Lowell Street, Tucson, Arizona 85721, USA)

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.

Suggested Citation

  • John A. Pezza & Janice Villali & Suzanne S. Sindi & Tricia R. Serio, 2014. "Amyloid-associated activity contributes to the severity and toxicity of a prion phenotype," Nature Communications, Nature, vol. 5(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5384
    DOI: 10.1038/ncomms5384
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