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5ffm

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Revision as of 19:25, 30 December 2015

Yellow fever virus helicase

Structural highlights

5ffm is a 1 chain structure. This structure supersedes the now removed PDB entry 1ymf. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Activity:	Flavivirin, with EC number 3.4.21.91
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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]

Publication Abstract from PubMed

Yellow fever virus (YFV), a member of the Flavivirus genus, has a plus-sense RNA genome encoding a single polyprotein. Viral protein NS3 includes a protease and a helicase that are essential to virus replication and to RNA capping. The 1.8-A crystal structure of the helicase region of the YFV NS3 protein includes residues 187 to 623. Two familiar helicase domains bind nucleotide in a triphosphate pocket without base recognition, providing a site for nonspecific hydrolysis of nucleoside triphosphates and RNA triphosphate. The third, C-terminal domain has a unique structure and is proposed to function in RNA and protein recognition. The organization of the three domains indicates that cleavage of the viral polyprotein NS3-NS4A junction occurs in trans.

Structure of the Flavivirus helicase: implications for catalytic activity, protein interactions, and proteolytic processing.,Wu J, Bera AK, Kuhn RJ, Smith JL J Virol. 2005 Aug;79(16):10268-77. PMID:16051820^[56]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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