4qbb

Structural highlights

Function

POLG_FMDVO The leader protease autocatalytically cleaves itself from the polyprotein at the L/VP0 junction. It also cleaves the host translation initiation factor EIF4G1 and EIF4G3, in order to shut down the capped cellular mRNA transcription.^{[1] [2] [3] [4]} 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. The capsid interacts with host heparan sulfate and various integrins (alphavbeta6, alphavbeta1, alphavbeta3, alpha5beta1, alphavbeta8) to provide virion attachment to target Attachment via host integrins induces virion internalization predominantly through clathrin-mediated endocytosis. In strains adapted to cell culture, attachment to heparan sulfate can also be used and induces virion internalization through clathrin- and caveolin-independent endocytosis.^{[5] [6] [7] [8]} Protein VP0: VP0 precursor is a component of immature procapsids (By similarity).^{[9] [10] [11] [12]} Protein 2B: Affects membrane integrity and cause an increase in membrane permeability (By similarity).^{[13] [14] [15] [16]} Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).^{[17] [18] [19] [20]} Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity).^{[21] [22] [23] [24]} Protein 3B-1, 3B-2 and 3B-3 are covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. They acts as a genome-linked replication primer (By similarity).^{[25] [26] [27] [28]} 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).^{[29] [30] [31] [32]} RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).^{[33] [34] [35] [36]}

See Also

• Virus protease 3D structures

References

1. ↑ Medina M, Domingo E, Brangwyn JK, Belsham GJ. The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities. Virology. 1993 May;194(1):355-9. PMID:8386879 doi:http://dx.doi.org/S0042-6822(83)71267-5
2. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
3. ↑ Gradi A, Foeger N, Strong R, Svitkin YV, Sonenberg N, Skern T, Belsham GJ. Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro. J Virol. 2004 Apr;78(7):3271-8. PMID:15016848
4. ↑ O'Donnell V, Larocco M, Baxt B. Heparan sulfate-binding foot-and-mouth disease virus enters cells via caveola-mediated endocytosis. J Virol. 2008 Sep;82(18):9075-85. doi: 10.1128/JVI.00732-08. Epub 2008 Jul 9. PMID:18614639 doi:http://dx.doi.org/10.1128/JVI.00732-08
5. ↑ Medina M, Domingo E, Brangwyn JK, Belsham GJ. The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities. Virology. 1993 May;194(1):355-9. PMID:8386879 doi:http://dx.doi.org/S0042-6822(83)71267-5
6. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
7. ↑ Gradi A, Foeger N, Strong R, Svitkin YV, Sonenberg N, Skern T, Belsham GJ. Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro. J Virol. 2004 Apr;78(7):3271-8. PMID:15016848
8. ↑ O'Donnell V, Larocco M, Baxt B. Heparan sulfate-binding foot-and-mouth disease virus enters cells via caveola-mediated endocytosis. J Virol. 2008 Sep;82(18):9075-85. doi: 10.1128/JVI.00732-08. Epub 2008 Jul 9. PMID:18614639 doi:http://dx.doi.org/10.1128/JVI.00732-08
9. ↑ Medina M, Domingo E, Brangwyn JK, Belsham GJ. The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities. Virology. 1993 May;194(1):355-9. PMID:8386879 doi:http://dx.doi.org/S0042-6822(83)71267-5
10. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
11. ↑ Gradi A, Foeger N, Strong R, Svitkin YV, Sonenberg N, Skern T, Belsham GJ. Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro. J Virol. 2004 Apr;78(7):3271-8. PMID:15016848
12. ↑ O'Donnell V, Larocco M, Baxt B. Heparan sulfate-binding foot-and-mouth disease virus enters cells via caveola-mediated endocytosis. J Virol. 2008 Sep;82(18):9075-85. doi: 10.1128/JVI.00732-08. Epub 2008 Jul 9. PMID:18614639 doi:http://dx.doi.org/10.1128/JVI.00732-08
13. ↑ Medina M, Domingo E, Brangwyn JK, Belsham GJ. The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities. Virology. 1993 May;194(1):355-9. PMID:8386879 doi:http://dx.doi.org/S0042-6822(83)71267-5
14. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
15. ↑ Gradi A, Foeger N, Strong R, Svitkin YV, Sonenberg N, Skern T, Belsham GJ. Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro. J Virol. 2004 Apr;78(7):3271-8. PMID:15016848
16. ↑ O'Donnell V, Larocco M, Baxt B. Heparan sulfate-binding foot-and-mouth disease virus enters cells via caveola-mediated endocytosis. J Virol. 2008 Sep;82(18):9075-85. doi: 10.1128/JVI.00732-08. Epub 2008 Jul 9. PMID:18614639 doi:http://dx.doi.org/10.1128/JVI.00732-08
17. ↑ Medina M, Domingo E, Brangwyn JK, Belsham GJ. The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities. Virology. 1993 May;194(1):355-9. PMID:8386879 doi:http://dx.doi.org/S0042-6822(83)71267-5
18. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
19. ↑ Gradi A, Foeger N, Strong R, Svitkin YV, Sonenberg N, Skern T, Belsham GJ. Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro. J Virol. 2004 Apr;78(7):3271-8. PMID:15016848
20. ↑ O'Donnell V, Larocco M, Baxt B. Heparan sulfate-binding foot-and-mouth disease virus enters cells via caveola-mediated endocytosis. J Virol. 2008 Sep;82(18):9075-85. doi: 10.1128/JVI.00732-08. Epub 2008 Jul 9. PMID:18614639 doi:http://dx.doi.org/10.1128/JVI.00732-08
21. ↑ Medina M, Domingo E, Brangwyn JK, Belsham GJ. The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities. Virology. 1993 May;194(1):355-9. PMID:8386879 doi:http://dx.doi.org/S0042-6822(83)71267-5
22. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
23. ↑ Gradi A, Foeger N, Strong R, Svitkin YV, Sonenberg N, Skern T, Belsham GJ. Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro. J Virol. 2004 Apr;78(7):3271-8. PMID:15016848
24. ↑ O'Donnell V, Larocco M, Baxt B. Heparan sulfate-binding foot-and-mouth disease virus enters cells via caveola-mediated endocytosis. J Virol. 2008 Sep;82(18):9075-85. doi: 10.1128/JVI.00732-08. Epub 2008 Jul 9. PMID:18614639 doi:http://dx.doi.org/10.1128/JVI.00732-08
25. ↑ Medina M, Domingo E, Brangwyn JK, Belsham GJ. The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities. Virology. 1993 May;194(1):355-9. PMID:8386879 doi:http://dx.doi.org/S0042-6822(83)71267-5
26. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
27. ↑ Gradi A, Foeger N, Strong R, Svitkin YV, Sonenberg N, Skern T, Belsham GJ. Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro. J Virol. 2004 Apr;78(7):3271-8. PMID:15016848
28. ↑ O'Donnell V, Larocco M, Baxt B. Heparan sulfate-binding foot-and-mouth disease virus enters cells via caveola-mediated endocytosis. J Virol. 2008 Sep;82(18):9075-85. doi: 10.1128/JVI.00732-08. Epub 2008 Jul 9. PMID:18614639 doi:http://dx.doi.org/10.1128/JVI.00732-08
29. ↑ Medina M, Domingo E, Brangwyn JK, Belsham GJ. The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities. Virology. 1993 May;194(1):355-9. PMID:8386879 doi:http://dx.doi.org/S0042-6822(83)71267-5
30. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
31. ↑ Gradi A, Foeger N, Strong R, Svitkin YV, Sonenberg N, Skern T, Belsham GJ. Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro. J Virol. 2004 Apr;78(7):3271-8. PMID:15016848
32. ↑ O'Donnell V, Larocco M, Baxt B. Heparan sulfate-binding foot-and-mouth disease virus enters cells via caveola-mediated endocytosis. J Virol. 2008 Sep;82(18):9075-85. doi: 10.1128/JVI.00732-08. Epub 2008 Jul 9. PMID:18614639 doi:http://dx.doi.org/10.1128/JVI.00732-08
33. ↑ Medina M, Domingo E, Brangwyn JK, Belsham GJ. The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities. Virology. 1993 May;194(1):355-9. PMID:8386879 doi:http://dx.doi.org/S0042-6822(83)71267-5
34. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
35. ↑ Gradi A, Foeger N, Strong R, Svitkin YV, Sonenberg N, Skern T, Belsham GJ. Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro. J Virol. 2004 Apr;78(7):3271-8. PMID:15016848
36. ↑ O'Donnell V, Larocco M, Baxt B. Heparan sulfate-binding foot-and-mouth disease virus enters cells via caveola-mediated endocytosis. J Virol. 2008 Sep;82(18):9075-85. doi: 10.1128/JVI.00732-08. Epub 2008 Jul 9. PMID:18614639 doi:http://dx.doi.org/10.1128/JVI.00732-08
37. ↑ Steinberger J, Grishkovskaya I, Cencic R, Juliano L, Juliano MA, Skern T. Foot-and-mouth disease virus leader proteinase: Structural insights into the mechanism of intermolecular cleavage. Virology. 2014 Sep 18;468-470C:397-408. doi: 10.1016/j.virol.2014.08.023. PMID:25240326 doi:http://dx.doi.org/10.1016/j.virol.2014.08.023