Mutations in the dimer interfaces of the dengue virus capsid protein affect structural stability and impair RNA-capsid interaction

Scientific Reports
Janaina Figueira-MansurRonaldo Mohana-Borges

Abstract

The dengue virus 2 capsid protein (DENV2C) plays a primary structural role in the protection of the viral genome and is crucial for nucleocapsid assembly. In this study, we generated single mutants of DENV2C at L50 and L54 residues of the α2 helix, which was shown to interfere with the integration of the capsid into lipid droplets, and at residues L81 and I88 located in the α4 helix, which was shown to affect viral assembly. We demonstrated that the oligomeric states of DENV2C and its mutants exist primarily in the dimeric state in solution. All single-point mutations introduced in DENV2C promoted reduction in protein stability, an effect that was more pronounced for the L81N and I88N mutants, but not protein unfolding. All the single-point mutations affected the ability of DEN2C to interact with RNA. We concluded that mutations in the α2-α2' and α4-α4' dimer interfaces of DENV2C affect the structural stability of the protein and impair RNA-capsid interaction. These effects were more pronounced for mutations at the L81 and I88 residues in the α4 helix. These results indicate the importance of the α4-α4' dimer interface, which could be studied as a potential target for drug design in the future.

References

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Citations

Mar 16, 2021·Current Opinion in Virology·Thais C Neves-MartinsAndrea T Da Poian
May 22, 2021·European Journal of Medicinal Chemistry·Akshatha H SManisha Singh
Aug 20, 2021·The Journal of General Virology·Sutha SangiambutPrida Malasit
Aug 15, 2021·The International Journal of Biochemistry & Cell Biology·Xiaodong WuGeng Dong
Aug 14, 2020·Biochimica Et Biophysica Acta. Biomembranes·Kumar Udit SaumyaRajanish Giri

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Methods Mentioned

BETA
nuclear magnetic resonance
NMR
circular dichroism
gel-filtration
fluorescence spectroscopy
Fluorescence
PCR
circular

Software Mentioned

MesReNova
GraphPad Prism

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