1yks

Structural highlights

Function

[POLG_YEFV1] Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA (By similarity).^{[1] [2] [3] [4] [5]} prM acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated (By similarity).^{[6] [7] [8] [9] [10]} Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).^{[11] [12] [13] [14] [15]} Non-structural protein 1 is involved in virus replication and regulation of the innate immune response (By similarity).^{[16] [17] [18] [19] [20]} Non-structural protein 2A may be involved viral RNA replication and capsid assembly (Potential).^{[21] [22] [23] [24] [25]} Non-structural protein 2B is a required cofactor for the serine protease function of NS3 (By similarity).^{[26] [27] [28] [29] [30]} Serine protease NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity).^{[31] [32] [33] [34] [35]} Non-structural protein 4A induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functioning as a replication complex. NS4A might also regulate the ATPase activity of the NS3 helicase (By similarity).^{[36] [37] [38] [39] [40]} Peptide 2k functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter (By similarity).^{[41] [42] [43] [44] [45]} Non-structural protein 4B inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway (By similarity).^{[46] [47] [48] [49] [50]} RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway (By similarity).^{[51] [52] [53] [54] [55]}

Evolutionary Conservation

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

References

1. ↑ Amberg SM, Nestorowicz A, McCourt DW, Rice CM. NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J Virol. 1994 Jun;68(6):3794-802. PMID:8189517
2. ↑ Lindenbach BD, Rice CM. trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol. 1997 Dec;71(12):9608-17. PMID:9371625
3. ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
4. ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
5. ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
6. ↑ Amberg SM, Nestorowicz A, McCourt DW, Rice CM. NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J Virol. 1994 Jun;68(6):3794-802. PMID:8189517
7. ↑ Lindenbach BD, Rice CM. trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol. 1997 Dec;71(12):9608-17. PMID:9371625
8. ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
9. ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
10. ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
11. ↑ Amberg SM, Nestorowicz A, McCourt DW, Rice CM. NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J Virol. 1994 Jun;68(6):3794-802. PMID:8189517
12. ↑ Lindenbach BD, Rice CM. trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol. 1997 Dec;71(12):9608-17. PMID:9371625
13. ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
14. ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
15. ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
16. ↑ Amberg SM, Nestorowicz A, McCourt DW, Rice CM. NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J Virol. 1994 Jun;68(6):3794-802. PMID:8189517
17. ↑ Lindenbach BD, Rice CM. trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol. 1997 Dec;71(12):9608-17. PMID:9371625
18. ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
19. ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
20. ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
21. ↑ Amberg SM, Nestorowicz A, McCourt DW, Rice CM. NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J Virol. 1994 Jun;68(6):3794-802. PMID:8189517
22. ↑ Lindenbach BD, Rice CM. trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol. 1997 Dec;71(12):9608-17. PMID:9371625
23. ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
24. ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
25. ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
26. ↑ Amberg SM, Nestorowicz A, McCourt DW, Rice CM. NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J Virol. 1994 Jun;68(6):3794-802. PMID:8189517
27. ↑ Lindenbach BD, Rice CM. trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol. 1997 Dec;71(12):9608-17. PMID:9371625
28. ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
29. ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
30. ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
31. ↑ Amberg SM, Nestorowicz A, McCourt DW, Rice CM. NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J Virol. 1994 Jun;68(6):3794-802. PMID:8189517
32. ↑ Lindenbach BD, Rice CM. trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol. 1997 Dec;71(12):9608-17. PMID:9371625
33. ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
34. ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
35. ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
36. ↑ Amberg SM, Nestorowicz A, McCourt DW, Rice CM. NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J Virol. 1994 Jun;68(6):3794-802. PMID:8189517
37. ↑ Lindenbach BD, Rice CM. trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol. 1997 Dec;71(12):9608-17. PMID:9371625
38. ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
39. ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
40. ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
41. ↑ Amberg SM, Nestorowicz A, McCourt DW, Rice CM. NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J Virol. 1994 Jun;68(6):3794-802. PMID:8189517
42. ↑ Lindenbach BD, Rice CM. trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol. 1997 Dec;71(12):9608-17. PMID:9371625
43. ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
44. ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
45. ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
46. ↑ Amberg SM, Nestorowicz A, McCourt DW, Rice CM. NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J Virol. 1994 Jun;68(6):3794-802. PMID:8189517
47. ↑ Lindenbach BD, Rice CM. trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol. 1997 Dec;71(12):9608-17. PMID:9371625
48. ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
49. ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
50. ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
51. ↑ Amberg SM, Nestorowicz A, McCourt DW, Rice CM. NS2B-3 proteinase-mediated processing in the yellow fever virus structural region: in vitro and in vivo studies. J Virol. 1994 Jun;68(6):3794-802. PMID:8189517
52. ↑ Lindenbach BD, Rice CM. trans-Complementation of yellow fever virus NS1 reveals a role in early RNA replication. J Virol. 1997 Dec;71(12):9608-17. PMID:9371625
53. ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
54. ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
55. ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
56. ↑ Wu J, Bera AK, Kuhn RJ, Smith JL. Structure of the Flavivirus helicase: implications for catalytic activity, protein interactions, and proteolytic processing. J Virol. 2005 Aug;79(16):10268-77. PMID:16051820 doi:79/16/10268