title: [Modification of [PSI+] prion properties by the combination of amino acid changes within Sup35 protein N-domain].
abstract: [PSI+] prion is an amyloid isoform of a release factor Sup35p (eRF3). The structure of these protein aggregates remains unclear despite a long term history of prion amyloids investigations. The N-terminal domain of Sup35p (which is responsible for a propagation of prion) shapes superpleated beta-structure, according to modern concepts. Recently we constructed five double mutations within SUP35 sequence encoding the N-terminal prion-forming domain and investigated properties of mutant proteins. Mutations sup35-M1 (YQ46-47KK) and sup35-M2 (QQ61-62KK) lead to [PSI+] prion loss, while other mutant alleles (sup35-M3 QQ70-71KK; sup35-M4 QQ80-81KK; sup35-M5 QQ89-90KK) maintained prion. For the detail analysis of effects of mutant alleles on Sup35p aggregation we characterized propagation and properties of [PSI] prion in yeast strains bearing different mutant allele combinations. The data obtained have refined a supposed organization of beta-sheets forming by different regions of Sup35p prion-forming domain within amyloid. Also we obtained evidences that mutant sup35-M2 and sup35-M4 alleles change structure of prion aggregates. The prion destabilization by these mutations possibly is connected with decrease of heteroaggregate fragmentation by chaperones.
authors: S A
authors: SA
authors: Bondarev
authors: E D
authors: ED
authors: Shirokolobova
authors: N P
authors: NP
authors: Trubitsyna
authors: G A
authors: GA
authors: Zhuravleva
mesh_terms: D000483:Alleles; D058227:Amyloidogenic Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010454:Peptide Termination Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D066329:Protein Aggregates; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D058227:Amyloidogenic Proteins; D018832:Molecular Chaperones; D010454:Peptide Termination Factors; D066329:Protein Aggregates; D020033:Protein Isoforms; D011994:Recombinant Proteins; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins