1tme

Structural highlights

Function

POLG_TMEVD Leader protein: promotes host NUP98 phosphorylation and blocks the export of host mRNA from the nucleus. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response. The leader protein also inhibit host interferon regulatory factor 3 (IRF3) dimerization, thereby blocking the transcriptional activation of IFN genes.^{[1] [2]} Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes (By similarity).^{[3] [4]} Protein VP0: VP0 precursor is a component of immature procapsids (By similarity).^{[5] [6]} Protein 2B: Affects membrane integrity and cause an increase in membrane permeability (By similarity).^{[7] [8]} Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).^{[9] [10]} Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity).^{[11] [12]} Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity).^{[13] [14]} RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).^{[15] [16]} Protein 2A: is involved in host translation shutoff. Nuclear localization is required for this function (By similarity).^{[17] [18]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Ricour C, Delhaye S, Hato SV, Olenyik TD, Michel B, van Kuppeveld FJ, Gustin KE, Michiels T. Inhibition of mRNA export and dimerization of interferon regulatory factor 3 by Theiler's virus leader protein. J Gen Virol. 2009 Jan;90(Pt 1):177-86. doi: 10.1099/vir.0.005678-0. PMID:19088287 doi:http://dx.doi.org/10.1099/vir.0.005678-0
2. ↑ Ricour C, Borghese F, Sorgeloos F, Hato SV, van Kuppeveld FJ, Michiels T. Random mutagenesis defines a domain of Theiler's virus leader protein that is essential for antagonism of nucleocytoplasmic trafficking and cytokine gene expression. J Virol. 2009 Nov;83(21):11223-32. doi: 10.1128/JVI.00829-09. Epub 2009 Aug 26. PMID:19710133 doi:http://dx.doi.org/10.1128/JVI.00829-09
3. ↑ Ricour C, Delhaye S, Hato SV, Olenyik TD, Michel B, van Kuppeveld FJ, Gustin KE, Michiels T. Inhibition of mRNA export and dimerization of interferon regulatory factor 3 by Theiler's virus leader protein. J Gen Virol. 2009 Jan;90(Pt 1):177-86. doi: 10.1099/vir.0.005678-0. PMID:19088287 doi:http://dx.doi.org/10.1099/vir.0.005678-0
4. ↑ Ricour C, Borghese F, Sorgeloos F, Hato SV, van Kuppeveld FJ, Michiels T. Random mutagenesis defines a domain of Theiler's virus leader protein that is essential for antagonism of nucleocytoplasmic trafficking and cytokine gene expression. J Virol. 2009 Nov;83(21):11223-32. doi: 10.1128/JVI.00829-09. Epub 2009 Aug 26. PMID:19710133 doi:http://dx.doi.org/10.1128/JVI.00829-09
5. ↑ Ricour C, Delhaye S, Hato SV, Olenyik TD, Michel B, van Kuppeveld FJ, Gustin KE, Michiels T. Inhibition of mRNA export and dimerization of interferon regulatory factor 3 by Theiler's virus leader protein. J Gen Virol. 2009 Jan;90(Pt 1):177-86. doi: 10.1099/vir.0.005678-0. PMID:19088287 doi:http://dx.doi.org/10.1099/vir.0.005678-0
6. ↑ Ricour C, Borghese F, Sorgeloos F, Hato SV, van Kuppeveld FJ, Michiels T. Random mutagenesis defines a domain of Theiler's virus leader protein that is essential for antagonism of nucleocytoplasmic trafficking and cytokine gene expression. J Virol. 2009 Nov;83(21):11223-32. doi: 10.1128/JVI.00829-09. Epub 2009 Aug 26. PMID:19710133 doi:http://dx.doi.org/10.1128/JVI.00829-09
7. ↑ Ricour C, Delhaye S, Hato SV, Olenyik TD, Michel B, van Kuppeveld FJ, Gustin KE, Michiels T. Inhibition of mRNA export and dimerization of interferon regulatory factor 3 by Theiler's virus leader protein. J Gen Virol. 2009 Jan;90(Pt 1):177-86. doi: 10.1099/vir.0.005678-0. PMID:19088287 doi:http://dx.doi.org/10.1099/vir.0.005678-0
8. ↑ Ricour C, Borghese F, Sorgeloos F, Hato SV, van Kuppeveld FJ, Michiels T. Random mutagenesis defines a domain of Theiler's virus leader protein that is essential for antagonism of nucleocytoplasmic trafficking and cytokine gene expression. J Virol. 2009 Nov;83(21):11223-32. doi: 10.1128/JVI.00829-09. Epub 2009 Aug 26. PMID:19710133 doi:http://dx.doi.org/10.1128/JVI.00829-09
9. ↑ Ricour C, Delhaye S, Hato SV, Olenyik TD, Michel B, van Kuppeveld FJ, Gustin KE, Michiels T. Inhibition of mRNA export and dimerization of interferon regulatory factor 3 by Theiler's virus leader protein. J Gen Virol. 2009 Jan;90(Pt 1):177-86. doi: 10.1099/vir.0.005678-0. PMID:19088287 doi:http://dx.doi.org/10.1099/vir.0.005678-0
10. ↑ Ricour C, Borghese F, Sorgeloos F, Hato SV, van Kuppeveld FJ, Michiels T. Random mutagenesis defines a domain of Theiler's virus leader protein that is essential for antagonism of nucleocytoplasmic trafficking and cytokine gene expression. J Virol. 2009 Nov;83(21):11223-32. doi: 10.1128/JVI.00829-09. Epub 2009 Aug 26. PMID:19710133 doi:http://dx.doi.org/10.1128/JVI.00829-09
11. ↑ Ricour C, Delhaye S, Hato SV, Olenyik TD, Michel B, van Kuppeveld FJ, Gustin KE, Michiels T. Inhibition of mRNA export and dimerization of interferon regulatory factor 3 by Theiler's virus leader protein. J Gen Virol. 2009 Jan;90(Pt 1):177-86. doi: 10.1099/vir.0.005678-0. PMID:19088287 doi:http://dx.doi.org/10.1099/vir.0.005678-0
12. ↑ Ricour C, Borghese F, Sorgeloos F, Hato SV, van Kuppeveld FJ, Michiels T. Random mutagenesis defines a domain of Theiler's virus leader protein that is essential for antagonism of nucleocytoplasmic trafficking and cytokine gene expression. J Virol. 2009 Nov;83(21):11223-32. doi: 10.1128/JVI.00829-09. Epub 2009 Aug 26. PMID:19710133 doi:http://dx.doi.org/10.1128/JVI.00829-09
13. ↑ Ricour C, Delhaye S, Hato SV, Olenyik TD, Michel B, van Kuppeveld FJ, Gustin KE, Michiels T. Inhibition of mRNA export and dimerization of interferon regulatory factor 3 by Theiler's virus leader protein. J Gen Virol. 2009 Jan;90(Pt 1):177-86. doi: 10.1099/vir.0.005678-0. PMID:19088287 doi:http://dx.doi.org/10.1099/vir.0.005678-0
14. ↑ Ricour C, Borghese F, Sorgeloos F, Hato SV, van Kuppeveld FJ, Michiels T. Random mutagenesis defines a domain of Theiler's virus leader protein that is essential for antagonism of nucleocytoplasmic trafficking and cytokine gene expression. J Virol. 2009 Nov;83(21):11223-32. doi: 10.1128/JVI.00829-09. Epub 2009 Aug 26. PMID:19710133 doi:http://dx.doi.org/10.1128/JVI.00829-09
15. ↑ Ricour C, Delhaye S, Hato SV, Olenyik TD, Michel B, van Kuppeveld FJ, Gustin KE, Michiels T. Inhibition of mRNA export and dimerization of interferon regulatory factor 3 by Theiler's virus leader protein. J Gen Virol. 2009 Jan;90(Pt 1):177-86. doi: 10.1099/vir.0.005678-0. PMID:19088287 doi:http://dx.doi.org/10.1099/vir.0.005678-0
16. ↑ Ricour C, Borghese F, Sorgeloos F, Hato SV, van Kuppeveld FJ, Michiels T. Random mutagenesis defines a domain of Theiler's virus leader protein that is essential for antagonism of nucleocytoplasmic trafficking and cytokine gene expression. J Virol. 2009 Nov;83(21):11223-32. doi: 10.1128/JVI.00829-09. Epub 2009 Aug 26. PMID:19710133 doi:http://dx.doi.org/10.1128/JVI.00829-09
17. ↑ Ricour C, Delhaye S, Hato SV, Olenyik TD, Michel B, van Kuppeveld FJ, Gustin KE, Michiels T. Inhibition of mRNA export and dimerization of interferon regulatory factor 3 by Theiler's virus leader protein. J Gen Virol. 2009 Jan;90(Pt 1):177-86. doi: 10.1099/vir.0.005678-0. PMID:19088287 doi:http://dx.doi.org/10.1099/vir.0.005678-0
18. ↑ Ricour C, Borghese F, Sorgeloos F, Hato SV, van Kuppeveld FJ, Michiels T. Random mutagenesis defines a domain of Theiler's virus leader protein that is essential for antagonism of nucleocytoplasmic trafficking and cytokine gene expression. J Virol. 2009 Nov;83(21):11223-32. doi: 10.1128/JVI.00829-09. Epub 2009 Aug 26. PMID:19710133 doi:http://dx.doi.org/10.1128/JVI.00829-09