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dc.contributor.authorChen, Buxinen_US
dc.date.accessioned2009-08-26T18:17:12Z
dc.date.available2009-08-26T18:17:12Z
dc.date.issued2008-07-07en_US
dc.identifier.urihttp://hdl.handle.net/1853/29762
dc.description.abstractPrions are self-perpetuating and, in most cases, aggregation-prone protein isoforms that transmit neurodegenerative diseases in mammals and control heritable traits in yeast. Prion conversion requires a very high level of identity of the interacting protein sequences. Decreased transmission of the prion state between divergent proteins is termed "species barrier" and was thought to occur due to the inability of divergent prion proteins to co-aggregate. Species barrier can be overcome in cross-species infections, for example from "mad cows" to humans. We studied the counterparts of yeast prion protein Sup35, originated from three different species of the Saccharomyces sensu stricto group and exhibiting the range of prion domain divergence that overlaps with the range of divergence observed among distant mammalian species. Heterologous Sup35 proteins co-aggregated in S. cerevisiae cells. However, in vivo cross-species prion conversion was decreased and in vitro polymerization was cross-inhibited in at least some heterologous combinations, thus demonstrating the existence of prion species barrier. Our data suggests that species-specificity of prion transmission is controlled at the level of conformational transition rather than co-aggregation. We have shown the Sup35 prion domain is sufficient for the species barrier among the S. sensu stricto species, and constructed SUP35 chimeric prion domains, combining the subregions of various origins Our data demonstrated in different cross-species combinations, different modules of prion domain play a crucial role in the controlling of species-specificity of prion transmission. One essential amino acid position has been identified in S. cerevisiae and S. paradoxus system. Our data support a model suggesting that identity of the short amyloidogenic sequences is crucial for the species barrier. Sup35 originated from three different species of the S. sensu stricto group were capable of forming a prion in S. cerevisiae. However, it was not known whether they are capable of generating and maintaining the prion state in the homologous cell environment. We have constructed the S. paradoxus and S. bayanus strains with appropriate markers, and we were able to demonstrate de novo [PSI+] formation in S. paradoxus but not in S. bayanus. Our data show that [PSI+] formation is not a unique property of S. cerevisiae.en_US
dc.publisherGeorgia Institute of Technologyen_US
dc.subjectSpecies barrieren_US
dc.subjectS. paradoxusen_US
dc.subjectS. cerevisiaeen_US
dc.subjectPrionen_US
dc.subjectS. bayanusen_US
dc.subject.lcshPrions
dc.subject.lcshPrion diseases
dc.subject.lcshYeast
dc.subject.lcshCommunicable diseases
dc.titlePrion species barrier at the short phylogenetic distances in the yeast modelen_US
dc.typeDissertationen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentBiologyen_US
dc.description.advisorCommittee Chair: Chernoff, Yury; Committee Member: Bommarius, Andreas; Committee Member: Doyle, Donald; Committee Member: Lobachev, Kirill; Committee Member: Yi, Soojinen_US


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