| Autor: |
Danilov, Lavrentii G., Matveenko, Andrew G., Ryzhkova, Varvara E., Belousov, Mikhail V., Poleshchuk, Olga I., Likholetova, Daria V., Sokolov, Petr A., Kasyanenko, Nina A., Kajava, Andrey V., Zhouravleva, Galina A., Bondarev, Stanislav A. |
| Předmět: |
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| Zdroj: |
Frontiers in Molecular Neuroscience; 11/19/2019, Vol. 12, p1-14, 14p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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