title: Design of a New [PSI+]-No-More Mutation in SUP35 With Strong Inhibitory Effect on the [PSI+] Prion Propagation
metadata.name: dc.contributor.author
metadata.value: Danilov, Lavrentii G
metadata.lang: -
metadata.name: dc.contributor.author
metadata.value: Matveenko, Andrew G
metadata.lang: -
metadata.name: dc.contributor.author
metadata.value: Ryzhkova, Varvara E
metadata.lang: -
metadata.name: dc.contributor.author
metadata.value: Belousov, Mikhail V
metadata.lang: -
metadata.name: dc.contributor.author
metadata.value: Poleshchuk, Olga I
metadata.lang: -
metadata.name: dc.contributor.author
metadata.value: Likholetova, Daria V
metadata.lang: -
metadata.name: dc.contributor.author
metadata.value: Sokolov, Petr A
metadata.lang: -
metadata.name: dc.contributor.author
metadata.value: Kasyanenko, Nina A
metadata.lang: -
metadata.name: dc.contributor.author
metadata.value: Kajava, Andrey V
metadata.lang: -
metadata.name: dc.contributor.author
metadata.value: Zhouravleva, Galina A
metadata.lang: -
metadata.name: dc.contributor.author
metadata.value: Bondarev, Stanislav A
metadata.lang: -
metadata.name: dc.date.accessioned
metadata.value: 2019-11-19T11:23:38Z
metadata.lang: -
metadata.name: dc.date.available
metadata.value: 2019-11-19T11:23:38Z
metadata.lang: -
metadata.name: dc.date.issued
metadata.value: 2019-11-19
metadata.lang: -
metadata.name: dc.identifier.citation
metadata.value: Danilov et al., 2019
metadata.lang: en_GB
metadata.name: dc.identifier.other
metadata.value: doi: 10.3389/fnmol.2019.00274
metadata.lang: -
metadata.name: dc.identifier.uri
metadata.value: http://hdl.handle.net/11701/16600
metadata.lang: -
metadata.name: dc.description.abstract
metadata.value: A number of [PSI+]-no-more (PNM) mutations, eliminating [PSI+] prion, were previously
  described in SUP35. In this study, we designed and analyzed a new PNM mutation
  based on the parallel in-register β-structure of Sup35 prion fibrils suggested by the
  known experimental data. In such an arrangement, substitution of non-charged residues
  by charged ones may destabilize the fibril structure. We introduced Q33K/A34K amino
  acid substitutions into the Sup35 protein, corresponding allele was called sup35-M0.
  The mutagenized residues were chosen based on ArchCandy in silico prediction of high
  inhibitory effect on the amyloidogenic potential of Sup35. The experiments confirmed that
  Sup35-M0 leads to the elimination of [PSI+] with high efficiency. Our data suggested that
  the elimination of the [PSI+] prion is associated with the decreased aggregation properties
  of the protein. The new mutation can induce the prion with very low efficiency and is able
  to propagate only weak [PSI+] prion variants. We also showed that Sup35-M0 protein
  co-aggregates with the wild-type Sup35 in vivo. Moreover, our data confirmed the utility
  of the strategy of substitution of non-charged residues by charged ones to design new
  mutations to inhibit a prion formation
metadata.lang: en_GB
metadata.name: dc.description.sponsorship
metadata.value: RFBR grant 19-04-00173, RFBR grant 17-54-150002, and PRC CNRS
  grant PRC1524,18-34-00536, RSF grant 18-14-00050
metadata.lang: en_GB
metadata.name: dc.language.iso
metadata.value: en
metadata.lang: en_GB
metadata.name: dc.publisher
metadata.value: Frontiers in Molecular Neuroscience
metadata.lang: en_GB
metadata.name: dc.relation.ispartofseries
metadata.value: 12;274
metadata.lang: -
metadata.name: dc.subject
metadata.value: [PSI+], amyloid, ArchCandy, prion, Saccharomyces cerevisiae, SUP35 mutation, superpleated-β-structure
metadata.lang: en_GB
metadata.name: dc.title
metadata.value: Design of a New [PSI+]-No-More Mutation in SUP35 With Strong Inhibitory Effect on the [PSI+] Prion Propagation
metadata.lang: en_GB
metadata.name: dc.title.alternative
metadata.value: New PNM Mutation in SUP35
metadata.lang: en_GB
metadata.name: dc.type
metadata.value: Article
metadata.lang: en_GB
metadata.name: dc.type
metadata.value: Working Paper
metadata.lang: en_GB
resources.filename: Danilov_et_al_2019.pdf
resources.url: https://dspace.spbu.ru/bitstream/11701/16600/1/Danilov_et_al_2019.pdf
resources.format: Adobe PDF
resources.size: 1,53 MB