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dc.contributor.authorLanglois, Christine R.
dc.contributor.authorPei, Fen
dc.contributor.authorSindi, Suzanne S.
dc.contributor.authorSerio, Tricia R.
dc.date.accessioned2017-03-03T19:04:46Z
dc.date.available2017-03-03T19:04:46Z
dc.date.issued2016-11-04
dc.identifier.citationDistinct Prion Domain Sequences Ensure Efficient Amyloid Propagation by Promoting Chaperone Binding or Processing In Vivo 2016, 12 (11):e1006417 PLOS Geneticsen
dc.identifier.issn1553-7404
dc.identifier.doi10.1371/journal.pgen.1006417
dc.identifier.urihttp://hdl.handle.net/10150/622767
dc.description.abstractPrions are a group of proteins that can adopt a spectrum of metastable conformations in vivo. These alternative states change protein function and are self-replicating and transmissible, creating protein-based elements of inheritance and infectivity. Prion conformational flexibility is encoded in the amino acid composition and sequence of the protein, which dictate its ability not only to form an ordered aggregate known as amyloid but also to maintain and transmit this structure in vivo. But, while we can effectively predict amyloid propensity in vitro, the mechanism by which sequence elements promote prion propagation in vivo remains unclear. In yeast, propagation of the [PSI+] prion, the amyloid form of the Sup35 protein, has been linked to an oligopeptide repeat region of the protein. Here, we demonstrate that this region is composed of separable functional elements, the repeats themselves and a repeat proximal region, which are both required for efficient prion propagation. Changes in the numbers of these elements do not alter the physical properties of Sup35 amyloid, but their presence promotes amyloid fragmentation, and therefore maintenance, by molecular chaperones. Rather than acting redundantly, our observations suggest that these sequence elements make complementary contributions to prion propagation, with the repeat proximal region promoting chaperone binding to and the repeats promoting chaperone processing of Sup35 amyloid.
dc.description.sponsorshipNIH/NIGMS [R01 GM069802, R35 GM118042]; CRL [F31 GM099383]en
dc.language.isoenen
dc.publisherPUBLIC LIBRARY SCIENCEen
dc.relation.urlhttp://dx.plos.org/10.1371/journal.pgen.1006417en
dc.rights© 2016 Langlois et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.en
dc.titleDistinct Prion Domain Sequences Ensure Efficient Amyloid Propagation by Promoting Chaperone Binding or Processing In Vivoen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Dept Mol & Cellular Biolen
dc.identifier.journalPLOS Geneticsen
dc.description.noteOpen Access Journal.en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
refterms.dateFOA2018-04-25T23:08:54Z
html.description.abstractPrions are a group of proteins that can adopt a spectrum of metastable conformations in vivo. These alternative states change protein function and are self-replicating and transmissible, creating protein-based elements of inheritance and infectivity. Prion conformational flexibility is encoded in the amino acid composition and sequence of the protein, which dictate its ability not only to form an ordered aggregate known as amyloid but also to maintain and transmit this structure in vivo. But, while we can effectively predict amyloid propensity in vitro, the mechanism by which sequence elements promote prion propagation in vivo remains unclear. In yeast, propagation of the [PSI+] prion, the amyloid form of the Sup35 protein, has been linked to an oligopeptide repeat region of the protein. Here, we demonstrate that this region is composed of separable functional elements, the repeats themselves and a repeat proximal region, which are both required for efficient prion propagation. Changes in the numbers of these elements do not alter the physical properties of Sup35 amyloid, but their presence promotes amyloid fragmentation, and therefore maintenance, by molecular chaperones. Rather than acting redundantly, our observations suggest that these sequence elements make complementary contributions to prion propagation, with the repeat proximal region promoting chaperone binding to and the repeats promoting chaperone processing of Sup35 amyloid.


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