Tick-borne encephalitis virus capsid protein induces translational shutoff as revealed by its structural–biological analysis

Selinger, Martin; Novotný, Radim; Sýs, Jakub; Roby, Justin A; Tykalová, Hana; Ranjani, Ganji Sri; Vancová, Marie; Jaklová, Kateřina; Kaufman, Filip; Bloom, Marshall E.; Zdráhal, Zbyněk; Grubhoffer, Libor; Forwood, Jade K.; Hrabal, Richard; Rumlová, Michaela; Štěrba, Ján

doi:10.1016/j.jbc.2022.102585

Cited by 5 publications

(19 citation statements)

References 80 publications

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“…The homology model of the full-length C protein from the Kuutsalo-14 strain was predicted using the I-TASSER server by using the structure of the truncated C protein (PDB: 7YWQ) as a template (S1B Fig) [34,[54][55][56][57]. The C-score of the homology model was -0.69 (on a scale of -5 to 2), indicating high confidence structure prediction [54][55][56].…”

Section: Purified C Protein Binds To Lipids With Negatively-charged H...mentioning

confidence: 99%

“…It initially has a C-terminal membrane-spanning anchor of 20 residues, which is cleaved by the viral NS2B-NS3 protease [29]. The mature form of TBEV C protein consists of 96 residues and it has a similar fold as the C proteins of other flaviviruses (S1 Fig) [30][31][32][33][34]. The TBEV C protein is mainly a dimer both in solution, and within the virion, although higher-order oligomerisation has been suggested to occur [34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

“…The mature form of TBEV C protein consists of 96 residues and it has a similar fold as the C proteins of other flaviviruses (S1 Fig) [30][31][32][33][34]. The TBEV C protein is mainly a dimer both in solution, and within the virion, although higher-order oligomerisation has been suggested to occur [34][35][36][37]. The C protein contains a flexible N-terminus (17 aa) and four α-helices (α 1-α 4 ), with dimerization occurring via antiparallel interactions of the α 2 and α 4 helices [7,[30][31][32][33][34]37,38].…”

Section: Introductionmentioning

confidence: 99%

“…The TBEV C protein is mainly a dimer both in solution, and within the virion, although higher-order oligomerisation has been suggested to occur [34][35][36][37]. The C protein contains a flexible N-terminus (17 aa) and four α-helices (α 1-α 4 ), with dimerization occurring via antiparallel interactions of the α 2 and α 4 helices [7,[30][31][32][33][34]37,38]. The α 4 helix contains multiple positively-charged residues, thought to form a charged surface responsible for nucleic acid binding [32,34,35,39].…”

Section: Introductionmentioning

confidence: 99%

“…The C protein contains a flexible N-terminus (17 aa) and four α-helices (α 1-α 4 ), with dimerization occurring via antiparallel interactions of the α 2 and α 4 helices [7,[30][31][32][33][34]37,38]. The α 4 helix contains multiple positively-charged residues, thought to form a charged surface responsible for nucleic acid binding [32,34,35,39]. The other side of the dimer (the α 2 helix or the N-terminus) may be important for nucleic acid or membrane binding, although this facet of C protein function remains under-studied [32,[40][41][42].…”

Section: Introductionmentioning

confidence: 99%

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Simultaneous membrane and RNA binding by tick-borne encephalitis virus capsid protein

et al. 2023

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Tick-borne encephalitis virus is an enveloped, pathogenic, RNA virus in the family Flaviviridae, genus Flavivirus. Viral particles are formed when the nucleocapsid, consisting of an RNA genome and multiple copies of the capsid protein, buds through the endoplasmic reticulum membrane and acquires the viral envelope and the associated proteins. The coordination of the nucleocapsid components to the sites of assembly and budding are poorly understood. Here, we investigate the interactions of the wild-type and truncated capsid proteins with membranes with biophysical methods and model membrane systems. We show that capsid protein initially binds membranes via electrostatic interactions with negatively-charged lipids, which is followed by membrane insertion. Additionally, we show that membrane-bound capsid protein can recruit viral genomic RNA. We confirm the biological relevance of the biophysical findings by using mass spectrometry to show that purified virions contain negatively-charged lipids. Our results suggest that nucleocapsid assembly is coordinated by negatively-charged membrane patches on the endoplasmic reticulum and that the capsid protein mediates direct contacts between the nucleocapsid and the membrane.

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Section: Purified C Protein Binds To Lipids With Negatively-charged H...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Simultaneous membrane and RNA binding by tick-borne encephalitis virus capsid protein

et al. 2023

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Intrinsic disorder in flaviviral capsid proteins and its role in pathogenesis

Sundar,

Umashankar,

Sankar

et al. 2024

J Biosci

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Intrinsic disorder in flaviviral capsid proteins and their role in pathogenesis

Sundar,

Umashankar,

Sankar

et al. 2023

Preprint

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A high level of disorder in many viral proteins is a direct consequence of their small genomes, which makes interaction with multiple binding partners a necessity for infection and pathogenicity. A segment of the flaviviral capsid protein, also known as the molecular recognition feature (MoRF), undergoes a disorder-to-order transition upon binding to several protein partners. In order to understand their role in pathogenesis, the MORFs were identified and their homology was studied. Despite the lack of sequence similarities, the docking studies of Cs with the host proteins indicate conserved interactions involving MORFs across members of the phylogenetic subclades. Additionally, it was observed from the protein-protein networks that some MoRFs preferentially bind proteins that are involved in specialized functions such as ribosome biogenesis. The findings point to the importance of the MoRFs in the flaviviral life cycle, with important consequences for disease progression and suppression of the host immune system. Potentially, they might have impacted the way flaviviruses evolved to infect varied hosts using multiple vectors.

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Tick-borne encephalitis virus capsid protein induces translational shutoff as revealed by its structural–biological analysis

Cited by 5 publications

References 80 publications

Simultaneous membrane and RNA binding by tick-borne encephalitis virus capsid protein

Simultaneous membrane and RNA binding by tick-borne encephalitis virus capsid protein

Intrinsic disorder in flaviviral capsid proteins and its role in pathogenesis

Intrinsic disorder in flaviviral capsid proteins and their role in pathogenesis

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