[PSI+] maintenance is dependent on the composition, not primary sequence, of the oligopeptide repeat domain.

[PSI(+)], the prion form of the yeast Sup35 protein, results from the structural conversion of Sup35 from a soluble form into an infectious amyloid form. The infectivity of prions is thought to result from chaperone-dependent fiber cleavage that breaks large prion fibers into smaller, inheritable pr...

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Main Authors: James A Toombs, Nathan M Liss, Kacy R Cobble, Zobaida Ben-Musa, Eric D Ross
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3132755?pdf=render
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spelling doaj-5b9b055c45a3419dbaea612b6f6255bc2020-11-25T02:16:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0167e2195310.1371/journal.pone.0021953[PSI+] maintenance is dependent on the composition, not primary sequence, of the oligopeptide repeat domain.James A ToombsNathan M LissKacy R CobbleZobaida Ben-MusaEric D Ross[PSI(+)], the prion form of the yeast Sup35 protein, results from the structural conversion of Sup35 from a soluble form into an infectious amyloid form. The infectivity of prions is thought to result from chaperone-dependent fiber cleavage that breaks large prion fibers into smaller, inheritable propagons. Like the mammalian prion protein PrP, Sup35 contains an oligopeptide repeat domain. Deletion analysis indicates that the oligopeptide repeat domain is critical for [PSI(+)] propagation, while a distinct region of the prion domain is responsible for prion nucleation. The PrP oligopeptide repeat domain can substitute for the Sup35 oligopeptide repeat domain in supporting [PSI(+)] propagation, suggesting a common role for repeats in supporting prion maintenance. However, randomizing the order of the amino acids in the Sup35 prion domain does not block prion formation or propagation, suggesting that amino acid composition is the primary determinant of Sup35's prion propensity. Thus, it is unclear what role the oligopeptide repeats play in [PSI(+)] propagation: the repeats could simply act as a non-specific spacer separating the prion nucleation domain from the rest of the protein; the repeats could contain specific compositional elements that promote prion propagation; or the repeats, while not essential for prion propagation, might explain some unique features of [PSI(+)]. Here, we test these three hypotheses and show that the ability of the Sup35 and PrP repeats to support [PSI(+)] propagation stems from their amino acid composition, not their primary sequences. Furthermore, we demonstrate that compositional requirements for the repeat domain are distinct from those of the nucleation domain, indicating that prion nucleation and propagation are driven by distinct compositional features.http://europepmc.org/articles/PMC3132755?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author James A Toombs
Nathan M Liss
Kacy R Cobble
Zobaida Ben-Musa
Eric D Ross
spellingShingle James A Toombs
Nathan M Liss
Kacy R Cobble
Zobaida Ben-Musa
Eric D Ross
[PSI+] maintenance is dependent on the composition, not primary sequence, of the oligopeptide repeat domain.
PLoS ONE
author_facet James A Toombs
Nathan M Liss
Kacy R Cobble
Zobaida Ben-Musa
Eric D Ross
author_sort James A Toombs
title [PSI+] maintenance is dependent on the composition, not primary sequence, of the oligopeptide repeat domain.
title_short [PSI+] maintenance is dependent on the composition, not primary sequence, of the oligopeptide repeat domain.
title_full [PSI+] maintenance is dependent on the composition, not primary sequence, of the oligopeptide repeat domain.
title_fullStr [PSI+] maintenance is dependent on the composition, not primary sequence, of the oligopeptide repeat domain.
title_full_unstemmed [PSI+] maintenance is dependent on the composition, not primary sequence, of the oligopeptide repeat domain.
title_sort [psi+] maintenance is dependent on the composition, not primary sequence, of the oligopeptide repeat domain.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2011-01-01
description [PSI(+)], the prion form of the yeast Sup35 protein, results from the structural conversion of Sup35 from a soluble form into an infectious amyloid form. The infectivity of prions is thought to result from chaperone-dependent fiber cleavage that breaks large prion fibers into smaller, inheritable propagons. Like the mammalian prion protein PrP, Sup35 contains an oligopeptide repeat domain. Deletion analysis indicates that the oligopeptide repeat domain is critical for [PSI(+)] propagation, while a distinct region of the prion domain is responsible for prion nucleation. The PrP oligopeptide repeat domain can substitute for the Sup35 oligopeptide repeat domain in supporting [PSI(+)] propagation, suggesting a common role for repeats in supporting prion maintenance. However, randomizing the order of the amino acids in the Sup35 prion domain does not block prion formation or propagation, suggesting that amino acid composition is the primary determinant of Sup35's prion propensity. Thus, it is unclear what role the oligopeptide repeats play in [PSI(+)] propagation: the repeats could simply act as a non-specific spacer separating the prion nucleation domain from the rest of the protein; the repeats could contain specific compositional elements that promote prion propagation; or the repeats, while not essential for prion propagation, might explain some unique features of [PSI(+)]. Here, we test these three hypotheses and show that the ability of the Sup35 and PrP repeats to support [PSI(+)] propagation stems from their amino acid composition, not their primary sequences. Furthermore, we demonstrate that compositional requirements for the repeat domain are distinct from those of the nucleation domain, indicating that prion nucleation and propagation are driven by distinct compositional features.
url http://europepmc.org/articles/PMC3132755?pdf=render
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