Novel NMR Assignment Strategy Reveals Structural Heterogeneity in Solution of the nsP3 HVD Domain of Venezuelan Equine Encephalitis Virus

Novel NMR Assignment Strategy Reveals Structural Heterogeneity in Solution of the nsP3 HVD Domain of Venezuelan Equine Encephalitis Virus Научная публикация

Журнал

Molecules
, E-ISSN: 1420-3049

Вых. Данные

Год: 2020, Том: 25, Номер: 24, Номер статьи : 5824;, Страниц : DOI: 10.3390/molecules25245824

Ключевые слова

IDP; MUSIC pulse sequences; NMR; nsP3; VEEV

Авторы

Agback Peter ¹ , Shernyukov Andrey ^1,2 , Dominguez Dominguez Francisco ³ , Agback Tatiana ¹ , Frolova Frolova Elena T. ³

Организации

1	Department of Molecular Sciences, Swedish University of Agricultural Sciences, P.O. Box 7015Uppsala SE-750 07, Sweden
2	Laboratory of Magnetic Radiospectroscopy, N.N. Vorozhtsov Institute of Organic Chemistry, SB RAS, Novosibirsk, 630090, Russian Federation
3	Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294-2170, USA

In recent years, intrinsically disordered proteins (IDPs) and disordered domains have attracted great attention. Many of them contain linear motifs that mediate interactions with other factors during formation of multicomponent protein complexes. NMR spectrometry is a valuable tool for characterizing this type of interactions on both amino acid (aa) and atomic levels. Alphaviruses encode a nonstructural protein nsP3, which drives viral replication complex assembly. nsP3 proteins contain over 200-aa-long hypervariable domains (HVDs), which exhibits no homology between different alphavirus species, are predicted to be intrinsically disordered and appear to be critical for alphavirus adaptation to different cells. Previously, we have shown that nsP3 HVD of chikungunya virus (CHIKV) is completely disordered with low tendency to form secondary structures in free form. In this new study, we used novel NMR approaches to assign the spectra for the nsP3 HVD of Venezuelan equine encephalitis virus (VEEV). The HVDs of CHIKV and VEEV have no homology but are both involved in replication complex assembly and function. We have found that VEEV nsP3 HVD is also mostly disordered but contains a short stable α-helix in its C-terminal fragment, which mediates interaction with the members of cellular Fragile X syndrome protein family. Our NMR data also suggest that VEEV HVD has several regions with tendency to form secondary structures.

Agback P. , Shernyukov A. , Dominguez D.F. , Agback T. , Frolova F.E.T.
Novel NMR Assignment Strategy Reveals Structural Heterogeneity in Solution of the nsP3 HVD Domain of Venezuelan Equine Encephalitis Virus

Molecules. 2020. V.25. N24. 5824; . DOI: 10.3390/molecules25245824 WOS Scopus РИНЦ OpenAlex

Полный текст от издателя

Опубликована online:

10 дек. 2020 г.

Web of science:	WOS:000603226500001
Scopus:	2-s2.0-85098533117
РИНЦ:	45039985
OpenAlex:	W3112091789

БД	Цитирований
Scopus	5
Web of science	5
OpenAlex	7