4o6b: Difference between revisions
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{{STRUCTURE_4o6b| PDB=4o6b | SCENE= }} | |||
===Dengue Type2 Virus Non-structural protein 1 (NS1) Form 1 crystal=== | |||
{{ABSTRACT_PUBMED_24505133}} | |||
The | ==Function== | ||
[[http://www.uniprot.org/uniprot/POLG_DEN26 POLG_DEN26]] 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).<ref>PMID:15956546</ref> <ref>PMID:16544248</ref> <ref>PMID:15944325</ref> <ref>PMID:19850911</ref> <ref>PMID:19754307</ref> <ref>PMID:19272179</ref> 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).<ref>PMID:15956546</ref> <ref>PMID:16544248</ref> <ref>PMID:15944325</ref> <ref>PMID:19850911</ref> <ref>PMID:19754307</ref> <ref>PMID:19272179</ref> Non-structural protein 1 is involved in virus replication and regulation of the innate immune response. Soluble and membrane-associated NS1 may activate human complement and induce host vascular leakage. This effect might explain the clinical manifestations of dengue hemorrhagic fever and dengue shock syndrome (By similarity).<ref>PMID:15956546</ref> <ref>PMID:16544248</ref> <ref>PMID:15944325</ref> <ref>PMID:19850911</ref> <ref>PMID:19754307</ref> <ref>PMID:19272179</ref> Non-structural protein 2A may be involved viral RNA replication and capsid assembly (Potential).<ref>PMID:15956546</ref> <ref>PMID:16544248</ref> <ref>PMID:15944325</ref> <ref>PMID:19850911</ref> <ref>PMID:19754307</ref> <ref>PMID:19272179</ref> Non-structural protein 2B is a required cofactor for the serine protease function of NS3 (By similarity).<ref>PMID:15956546</ref> <ref>PMID:16544248</ref> <ref>PMID:15944325</ref> <ref>PMID:19850911</ref> <ref>PMID:19754307</ref> <ref>PMID:19272179</ref> 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).<ref>PMID:15956546</ref> <ref>PMID:16544248</ref> <ref>PMID:15944325</ref> <ref>PMID:19850911</ref> <ref>PMID:19754307</ref> <ref>PMID:19272179</ref> 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).<ref>PMID:15956546</ref> <ref>PMID:16544248</ref> <ref>PMID:15944325</ref> <ref>PMID:19850911</ref> <ref>PMID:19754307</ref> <ref>PMID:19272179</ref> Peptide 2k functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter (By similarity).<ref>PMID:15956546</ref> <ref>PMID:16544248</ref> <ref>PMID:15944325</ref> <ref>PMID:19850911</ref> <ref>PMID:19754307</ref> <ref>PMID:19272179</ref> 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.<ref>PMID:15956546</ref> <ref>PMID:16544248</ref> <ref>PMID:15944325</ref> <ref>PMID:19850911</ref> <ref>PMID:19754307</ref> <ref>PMID:19272179</ref> 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. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway (By similarity).<ref>PMID:15956546</ref> <ref>PMID:16544248</ref> <ref>PMID:15944325</ref> <ref>PMID:19850911</ref> <ref>PMID:19754307</ref> <ref>PMID:19272179</ref> Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA (By similarity).<ref>PMID:15956546</ref> <ref>PMID:16544248</ref> <ref>PMID:15944325</ref> <ref>PMID:19850911</ref> <ref>PMID:19754307</ref> <ref>PMID:19272179</ref> | |||
==About this Structure== | |||
[[4o6b]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O6B OCA]. | |||
==Reference== | |||
<ref group="xtra">PMID:024505133</ref><references group="xtra"/><references/> | |||
[[Category: Akey, D L.]] | |||
[[Category: Smith, J L.]] | |||
[[Category: Flavivirus]] | |||
[[Category: Non-structural protein 1]] | |||
[[Category: Ns1]] | |||
[[Category: Viral protein]] | |||