Title:
Pathogenic Polyglutamine Tracts Are Potent Inducers of Spontaneous Sup35 and Rnq1 Amyloidogenesis
Pathogenic Polyglutamine Tracts Are Potent Inducers of Spontaneous Sup35 and Rnq1 Amyloidogenesis
| dc.contributor.author | Goehler, Heike | en_US |
| dc.contributor.author | Dröge, Anja | en_US |
| dc.contributor.author | Lurz, Rudi | en_US |
| dc.contributor.author | Schnoegl, Sigrid | en_US |
| dc.contributor.author | Chernoff, Yury O. | en_US |
| dc.contributor.author | Wanker, Erich E. | en_US |
| dc.contributor.corporatename | Max-Delbrück-Centrum für Molekulare Medizin | en_US |
| dc.contributor.corporatename | Georgia Institute of Technology. School of Biology | en_US |
| dc.contributor.corporatename | Georgia Institute of Technology. Institute for Bioengineering and Bioscience | en_US |
| dc.date.accessioned | 2010-06-15T19:53:19Z | |
| dc.date.available | 2010-06-15T19:53:19Z | |
| dc.date.issued | 2010-03-10 | |
| 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 credited | en_US |
| dc.description | DOI:10.1371/journal.pone.0009642 | en_US |
| dc.description.abstract | The 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.identifier.citation | Heike 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), e9642 | en_US |
| dc.identifier.doi | 10.1371/journal.pone.0009642 | |
| dc.identifier.issn | 1932-6203 | |
| dc.identifier.uri | http://hdl.handle.net/1853/34011 | |
| dc.language.iso | en_US | en_US |
| dc.publisher | Georgia Institute of Technology | en_US |
| dc.publisher.original | Public Library of Science | |
| dc.subject | Yeasts | en_US |
| dc.subject | Prions | en_US |
| dc.subject | Amyloids | en_US |
| dc.subject | Protein aggregates | en_US |
| dc.subject | Amyloidogenesis | en_US |
| dc.title | Pathogenic Polyglutamine Tracts Are Potent Inducers of Spontaneous Sup35 and Rnq1 Amyloidogenesis | en_US |
| dc.type | Text | |
| dc.type.genre | Article | |
| dspace.entity.type | Publication | |
| local.contributor.author | Chernoff, Yury O. | |
| local.contributor.corporatename | College of Sciences | |
| local.contributor.corporatename | School of Biological Sciences | |
| relation.isAuthorOfPublication | d9f3d192-f4c7-4db2-ace4-2baadbeb98b6 | |
| relation.isOrgUnitOfPublication | 85042be6-2d68-4e07-b384-e1f908fae48a | |
| relation.isOrgUnitOfPublication | c8b3bd08-9989-40d3-afe3-e0ad8d5c72b5 |