Extensive diversity of prion strains is defined by differential chaperone interactions and distinct amyloidogenic regions.

Amyloidogenic proteins associated with a variety of unrelated diseases are typically capable of forming several distinct self-templating conformers. In prion diseases, these different structures, called prion strains (or variants), confer dramatic variation in disease pathology and transmission. Agg...

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Autores principales:	Kevin C Stein, Heather L True
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/4ed89be211c245d1ab6bca0bc7f81b76
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spelling	oai:doaj.org-article:4ed89be211c245d1ab6bca0bc7f81b762021-11-18T06:20:47ZExtensive diversity of prion strains is defined by differential chaperone interactions and distinct amyloidogenic regions.1553-73901553-740410.1371/journal.pgen.1004337https://doaj.org/article/4ed89be211c245d1ab6bca0bc7f81b762014-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24811344/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Amyloidogenic proteins associated with a variety of unrelated diseases are typically capable of forming several distinct self-templating conformers. In prion diseases, these different structures, called prion strains (or variants), confer dramatic variation in disease pathology and transmission. Aggregate stability has been found to be a key determinant of the diverse pathological consequences of different prion strains. Yet, it remains largely unclear what other factors might account for the widespread phenotypic variation seen with aggregation-prone proteins. Here, we examined a set of yeast prion variants of the [RNQ+] prion that differ in their ability to induce the formation of another yeast prion called [PSI+]. Remarkably, we found that the [RNQ+] variants require different, non-contiguous regions of the Rnq1 protein for both prion propagation and [PSI+] induction. This included regions outside of the canonical prion-forming domain of Rnq1. Remarkably, such differences did not result in variation in aggregate stability. Our analysis also revealed a striking difference in the ability of these [RNQ+] variants to interact with the chaperone Sis1. Thus, our work shows that the differential influence of various amyloidogenic regions and interactions with host cofactors are critical determinants of the phenotypic consequences of distinct aggregate structures. This helps reveal the complex interdependent factors that influence how a particular amyloid structure may dictate disease pathology and progression.Kevin C SteinHeather L TruePublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 10, Iss 5, p e1004337 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Kevin C Stein Heather L True Extensive diversity of prion strains is defined by differential chaperone interactions and distinct amyloidogenic regions.
description	Amyloidogenic proteins associated with a variety of unrelated diseases are typically capable of forming several distinct self-templating conformers. In prion diseases, these different structures, called prion strains (or variants), confer dramatic variation in disease pathology and transmission. Aggregate stability has been found to be a key determinant of the diverse pathological consequences of different prion strains. Yet, it remains largely unclear what other factors might account for the widespread phenotypic variation seen with aggregation-prone proteins. Here, we examined a set of yeast prion variants of the [RNQ+] prion that differ in their ability to induce the formation of another yeast prion called [PSI+]. Remarkably, we found that the [RNQ+] variants require different, non-contiguous regions of the Rnq1 protein for both prion propagation and [PSI+] induction. This included regions outside of the canonical prion-forming domain of Rnq1. Remarkably, such differences did not result in variation in aggregate stability. Our analysis also revealed a striking difference in the ability of these [RNQ+] variants to interact with the chaperone Sis1. Thus, our work shows that the differential influence of various amyloidogenic regions and interactions with host cofactors are critical determinants of the phenotypic consequences of distinct aggregate structures. This helps reveal the complex interdependent factors that influence how a particular amyloid structure may dictate disease pathology and progression.
format	article
author	Kevin C Stein Heather L True
author_facet	Kevin C Stein Heather L True
author_sort	Kevin C Stein
title	Extensive diversity of prion strains is defined by differential chaperone interactions and distinct amyloidogenic regions.
title_short	Extensive diversity of prion strains is defined by differential chaperone interactions and distinct amyloidogenic regions.
title_full	Extensive diversity of prion strains is defined by differential chaperone interactions and distinct amyloidogenic regions.
title_fullStr	Extensive diversity of prion strains is defined by differential chaperone interactions and distinct amyloidogenic regions.
title_full_unstemmed	Extensive diversity of prion strains is defined by differential chaperone interactions and distinct amyloidogenic regions.
title_sort	extensive diversity of prion strains is defined by differential chaperone interactions and distinct amyloidogenic regions.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/4ed89be211c245d1ab6bca0bc7f81b76
work_keys_str_mv	AT kevincstein extensivediversityofprionstrainsisdefinedbydifferentialchaperoneinteractionsanddistinctamyloidogenicregions AT heatherltrue extensivediversityofprionstrainsisdefinedbydifferentialchaperoneinteractionsanddistinctamyloidogenicregions
_version_	1718424477364125696

Extensive diversity of prion strains is defined by differential chaperone interactions and distinct amyloidogenic regions.

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