Aggregation of Influenza A Virus Nuclear Export Protein
- Autores: Golovko A.1, Koroleva O.2, Tolstova A.3, Kuz’mina N.4,5, Dubrovin E.3, Drutsa V.6
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Afiliações:
- Department of Bioengineering and Bioinformatics
- Department of Chemistry
- Department of Physics
- Department of Biology
- Frumkin Institute of Physical Chemistry and Electrochemistry
- Belozersky Research Institute of Physico-Chemical Biology
- Edição: Volume 83, Nº 11 (2018)
- Páginas: 1411-1421
- Seção: Article
- URL: https://journals.rcsi.science/0006-2979/article/view/151763
- DOI: https://doi.org/10.1134/S0006297918110111
- ID: 151763
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Resumo
Influenza A virus nuclear export protein (NEP) plays an important role in the viral life cycle. Recombinant NEP proteins containing (His)6-tag at either N-or C-terminus were obtained by heterologous expression in Escherichia coli cells and their high propensity for aggregation was demonstrated. Dynamic light scattering technique was used to study the kinetics and properties of NEP aggregation in solutions under different conditions (pH, ionic strength, presence of low-molecular-weight additives and organic solvents). Using atomic force microscopy, the predominance of spherical aggregates in all examined NEP preparations was shown, with some amyloid-like structures being observed in the case of NEP-C protein. A number of structure prediction programs were used to identify aggregation-prone regions in the NEP structure. All-atom molecular dynamics simulations indicate a high rate of NEP molecule aggregation and reveal the regions preferentially involved in the intermolecular contacts that are located at the edges of the rod-like protein molecule. Our results suggest that NEP aggregation is determined by different types of interactions and represents an intrinsic property of the protein that appears to be necessary for its functioning in vivo.
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Sobre autores
A. Golovko
Department of Bioengineering and Bioinformatics
Email: koroleva@genebee.msu.ru
Rússia, Moscow, 119991
O. Koroleva
Department of Chemistry
Autor responsável pela correspondência
Email: koroleva@genebee.msu.ru
Rússia, Moscow, 119991
A. Tolstova
Department of Physics
Email: koroleva@genebee.msu.ru
Rússia, Moscow, 119991
N. Kuz’mina
Department of Biology; Frumkin Institute of Physical Chemistry and Electrochemistry
Email: koroleva@genebee.msu.ru
Rússia, Moscow, 119991; Moscow, 119071
E. Dubrovin
Department of Physics
Email: koroleva@genebee.msu.ru
Rússia, Moscow, 119991
V. Drutsa
Belozersky Research Institute of Physico-Chemical Biology
Email: koroleva@genebee.msu.ru
Rússia, Moscow, 119991