Extensive Diversity of Prion Strains Is Defined by Differential Chaperone Interactions and Distinct Amyloidogenic Regions

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Protein conformational disorders, including many neurodegenerative diseases, result when a protein misfolds and undergoes a conformational change to form self-templating aggregates, called amyloid. Interestingly, the proteins that misfold in these diseases tend to form a wide variety of distinct aggregate structures. In prion diseases, these different amyloid conformations are called prion strains. The different conformations of prion strains are responsible for modulating disease progression, pathology, and transmission. Previous work with yeast prions has provided tremendous insight into how distinct prion conformers can cause such phenotypic variability. Here, we used a set of [RNQ+] prion variants to show the complex web of interactions involved in the propagation of distinct aggregate structures. We found that several different non-adjacent regions of Rnq1, even outside the prion-forming domain, make varying contributions to the propagation of distinct variants of the [RNQ+] prion. Moreover, our data support the hypothesis that the [RNQ+] variants differentially interact with the molecular chaperone Sis1. These data strongly suggest that the variable phenotypic manifestations of different aggregate conformations depend upon a unique set of primary structural elements and differential interactions with host cofactors.

Vyšlo v časopise: Extensive Diversity of Prion Strains Is Defined by Differential Chaperone Interactions and Distinct Amyloidogenic Regions. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004337
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004337

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