| SELINGER, Martin, Radim NOVOTNY, Jakub SYS, Justin A ROBY, Hana TYKALOVA, Sri Ranjani GANJI, Marie VANCOVA, Katerina JAKLOVA, Filip KAUFMAN, Marshall E BLOOM, Zbyněk ZDRÁHAL, Libor GRUBHOFFER, Jade K FORWOOD, Richard HRABAL, Michaela RUMLOVA and Jan STERBA. Tick-borne encephalitis virus capsid protein induces translational shutoff as revealed by its structural-biological analysis. JOURNAL OF BIOLOGICAL CHEMISTRY. ELSEVIER, 2022, vol. 298, No 11, p. 102585-102608. ISSN 1083-351X. Available from: https://dx.doi.org/10.1016/j.jbc.2022.102585. |
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@article{2265638,
author = {Selinger, Martin and Novotny, Radim and Sys, Jakub and Roby, Justin A and Tykalova, Hana and Ganji, Sri Ranjani and Vancova, Marie and Jaklova, Katerina and Kaufman, Filip and Bloom, Marshall E and Zdráhal, Zbyněk and Grubhoffer, Libor and Forwood, Jade K and Hrabal, Richard and Rumlova, Michaela and Sterba, Jan},
article_number = {11},
doi = {http://dx.doi.org/10.1016/j.jbc.2022.102585},
keywords = {Capsid; Capsid Proteins; Encephalitis Viruses; Tick-Borne; RNA; Viral Nonstructural Proteins},
language = {eng},
issn = {1083-351X},
journal = {JOURNAL OF BIOLOGICAL CHEMISTRY},
title = {Tick-borne encephalitis virus capsid protein induces translational shutoff as revealed by its structural-biological analysis},
url = {https://www.sciencedirect.com/science/article/pii/S0021925822010286?via%3Dihub},
volume = {298},
year = {2022}
}
TY - JOUR
ID - 2265638
AU - Selinger, Martin - Novotny, Radim - Sys, Jakub - Roby, Justin A - Tykalova, Hana - Ganji, Sri Ranjani - Vancova, Marie - Jaklova, Katerina - Kaufman, Filip - Bloom, Marshall E - Zdráhal, Zbyněk - Grubhoffer, Libor - Forwood, Jade K - Hrabal, Richard - Rumlova, Michaela - Sterba, Jan
PY - 2022
TI - Tick-borne encephalitis virus capsid protein induces translational shutoff as revealed by its structural-biological analysis
JF - JOURNAL OF BIOLOGICAL CHEMISTRY
VL - 298
IS - 11
SP - 102585
EP - 102585
PB - ELSEVIER
SN - 1083351X
KW - Capsid
KW - Capsid Proteins
KW - Encephalitis Viruses
KW - Tick-Borne
KW - RNA
KW - Viral Nonstructural Proteins
UR - https://www.sciencedirect.com/science/article/pii/S0021925822010286?via%3Dihub
N2 - Tick-borne encephalitis virus (TBEV) is the most medically relevant tick-transmitted Flavivirus in Eurasia, targeting the host central nervous system and frequently causing severe encephalitis. The primary function of its capsid protein (TBEVC) is to recruit the viral RNA and form a nucleocapsid. Additional functionality of Flavivirus capsid proteins has been documented, but further investigation is needed for TBEVC. Here, we show the first capsid protein 3D structure of a member of the tick-borne flaviviruses group. The structure of monomeric Δ16-TBEVC was determined using high-resolution multidimensional NMR spectroscopy. Based on natural in vitro TBEVC homodimerization, the dimeric interfaces were identified by hydrogen deuterium exchange mass spectrometry (MS). Although the assembly of flaviviruses occurs in endoplasmic reticulum–derived vesicles, we observed that TBEVC protein also accumulated in the nuclei and nucleoli of infected cells. In addition, the predicted bipartite nuclear localization sequence in the TBEVC C-terminal part was confirmed experimentally, and we described the interface between TBEVC bipartite nuclear localization sequence and import adapter protein importin-alpha using X-ray crystallography. Furthermore, our coimmunoprecipitation coupled with MS identification revealed 214 interaction partners of TBEVC, including viral envelope and nonstructural NS5 proteins and a wide variety of host proteins involved mainly in rRNA processing and translation initiation. Metabolic labeling experiments further confirmed that TBEVC and other flaviviral capsid proteins are able to induce translational shutoff and decrease of 18S rRNA. These findings may substantially help to design a targeted therapy against TBEV.
ER -
SELINGER, Martin, Radim NOVOTNY, Jakub SYS, Justin A ROBY, Hana TYKALOVA, Sri Ranjani GANJI, Marie VANCOVA, Katerina JAKLOVA, Filip KAUFMAN, Marshall E BLOOM, Zbyněk ZDRÁHAL, Libor GRUBHOFFER, Jade K FORWOOD, Richard HRABAL, Michaela RUMLOVA and Jan STERBA. Tick-borne encephalitis virus capsid protein induces translational shutoff as revealed by its structural-biological analysis. \textit{JOURNAL OF BIOLOGICAL CHEMISTRY}. ELSEVIER, 2022, vol.~298, No~11, p.~102585-102608. ISSN~1083-351X. Available from: https://dx.doi.org/10.1016/j.jbc.2022.102585.
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