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== | ==Crystal structure of the dengue 2 virus envelope protein in complex with n-octyl-beta-D-glucoside== | ||
Dengue virus is an emerging global health threat. Its major envelope | <StructureSection load='1oke' size='340' side='right'caption='[[1oke]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1oke]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_2 Dengue virus 2]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1oam 1oam]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OKE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OKE FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1oke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oke OCA], [https://pdbe.org/1oke PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oke RCSB], [https://www.ebi.ac.uk/pdbsum/1oke PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oke ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/POLG_DEN2P POLG_DEN2P] Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA (By similarity). 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 (By similarity). 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). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Dengue virus is an emerging global health threat. Its major envelope glycoprotein, E, mediates viral attachment and entry by membrane fusion. A crystal structure of the soluble ectodomain of E from dengue virus type 2 reveals a hydrophobic pocket lined by residues that influence the pH threshold for fusion. The pocket, which accepts a hydrophobic ligand, opens and closes through a conformational shift in a beta-hairpin at the interface between two domains. These features point to a structural pathway for the fusion-activating transition and suggest a strategy for finding small-molecule inhibitors of dengue and other flaviviruses. | |||
A ligand-binding pocket in the dengue virus envelope glycoprotein.,Modis Y, Ogata S, Clements D, Harrison SC Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):6986-91. Epub 2003 May 20. PMID:12759475<ref>PMID:12759475</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: Dengue virus | <div class="pdbe-citations 1oke" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Harrison | <references/> | ||
[[Category: Modis | __TOC__ | ||
</StructureSection> | |||
[[Category: Dengue virus 2]] | |||
[[Category: Large Structures]] | |||
[[Category: Harrison SC]] | |||
[[Category: Modis Y]] | |||