4o6b

Dengue Type2 Virus Non-structural protein 1 (NS1) Form 1 crystal

spinqualitylabelsall models 4o6b, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4o6b is a 2 chain structure with sequence from Dengue virus 2 Thailand/16681/84. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.0005Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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). 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). 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). Non-structural protein 2A may be involved viral RNA replication and capsid assembly (Potential). Non-structural protein 2B is a required cofactor for the serine protease function of NS3 (By similarity). 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). 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). Peptide 2k functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter (By similarity). 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. 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). Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA (By similarity). Publication Abstract from PubMed Flaviviruses, the human pathogens responsible for dengue fever, West Nile fever, tick-borne encephalitis and yellow fever, are endemic in tropical and temperate parts of the world. The flavivirus non-structural protein 1 (NS1) functions in genome replication as an intracellular dimer and in immune system evasion as a secreted hexamer. We report crystal structures for full-length, glycosylated NS1 from West Nile and dengue viruses. The NS1 hexamer in crystal structures is similar to a solution hexamer visualized by single-particle electron microscopy. Recombinant NS1 binds to lipid bilayers and remodels large liposomes into lipoprotein nano-particles. The NS1 structures reveal distinct domains for membrane association of the dimer and interactions with the immune system, and are a basis for elucidating the molecular mechanism of NS1 function. Flavivirus NS1 Structures Reveal Surfaces for Associations with Membranes and the Immune System.,Akey DL, Brown WC, Dutta S, Konwerski J, Jose J, Jurkiw TJ, Delproposto J, Ogata CM, Skiniotis G, Kuhn RJ, Smith JL Science. 2014 Feb 6. PMID:24505133 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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