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dc.contributor.authorGoehler, Heikeen_US
dc.contributor.authorDröge, Anjaen_US
dc.contributor.authorLurz, Rudien_US
dc.contributor.authorSchnoegl, Sigriden_US
dc.contributor.authorChernoff, Yury O.en_US
dc.contributor.authorWanker, Erich E.en_US
dc.date.accessioned2010-06-15T19:53:19Z
dc.date.available2010-06-15T19:53:19Z
dc.date.issued2010-03-10
dc.identifier.citationHeike Goehler, Anja Dröge, Rudi Lurz, Sigrid Schnoegl, Yury O. Chernoff, and Erich E. Wanker, "Pathogenic Polyglutamine Tracts Are Potent Inducers of Spontaneous Sup35 and Rnq1 Amyloidogenesis," PLoS ONE 5(3), e9642en_US
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/1853/34011
dc.description© 2010 Goehler et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. unrestricted use, distribution, and reproduction in any medium, provided the original author and source are crediteden_US
dc.descriptionDOI:10.1371/journal.pone.0009642en_US
dc.description.abstractThe glutamine/asparagine (Q/N)-rich yeast prion protein Sup35 has a low intrinsic propensity to spontaneously self-assemble into ordered, β-sheet-rich amyloid fibrils. In yeast cells, de novo formation of Sup35 aggregates is greatly facilitated by high protein concentrations and the presence of preformed Q/N-rich protein aggregates that template Sup35 polymerization. Here, we have investigated whether aggregation-promoting polyglutamine (polyQ) tracts can stimulate the de novo formation of ordered Sup35 protein aggregates in the absence of Q/N-rich yeast prions. Fusion proteins with polyQ tracts of different lengths were produced and their ability to spontaneously self-assemble into amlyloid structures was analyzed using in vitro and in vivo model systems. We found that Sup35 fusions with pathogenic (≥54 glutamines), as opposed to non-pathogenic (19 glutamines) polyQ tracts efficiently form seeding-competent protein aggregates. Strikingly, polyQ-mediated de novo assembly of Sup35 protein aggregates in yeast cells was independent of pre-existing Q/N-rich protein aggregates. This indicates that increasing the content of aggregation-promoting sequences enhances the tendency of Sup35 to spontaneously self-assemble into insoluble protein aggregates. A similar result was obtained when pathogenic polyQ tracts were linked to the yeast prion protein Rnq1, demonstrating that polyQ sequences are generic inducers of amyloidogenesis. In conclusion, long polyQ sequences are powerful molecular tools that allow the efficient production of seeding-competent amyloid structures.en_US
dc.language.isoen_USen_US
dc.publisherGeorgia Institute of Technologyen_US
dc.subjectYeastsen_US
dc.subjectPrionsen_US
dc.subjectAmyloidsen_US
dc.subjectProtein aggregatesen_US
dc.subjectAmyloidogenesisen_US
dc.titlePathogenic Polyglutamine Tracts Are Potent Inducers of Spontaneous Sup35 and Rnq1 Amyloidogenesisen_US
dc.typeArticleen_US
dc.contributor.corporatenameMax-Delbrück-Centrum für Molekulare Medizinen_US
dc.contributor.corporatenameGeorgia Institute of Technology. School of Biologyen_US
dc.contributor.corporatenameGeorgia Institute of Technology. Institute for Bioengineering and Bioscienceen_US
dc.publisher.originalPublic Library of Science
dc.identifier.doi10.1371/journal.pone.0009642


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