2jlv: Difference between revisions
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< | ==Dengue virus 4 NS3 helicase in complex with ssRNA and AMPPNP== | ||
<StructureSection load='2jlv' size='340' side='right'caption='[[2jlv]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2jlv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_4_Thailand/0348/1991 Dengue virus 4 Thailand/0348/1991]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JLV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JLV FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | |||
--> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=2jlv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jlv OCA], [https://pdbe.org/2jlv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jlv RCSB], [https://www.ebi.ac.uk/pdbsum/2jlv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jlv ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/POLG_DEN4T POLG_DEN4T] 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). | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jl/2jlv_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2jlv ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Together with the NS5 polymerase, the NS3 helicase has a pivotal function in flavivirus RNA replication and constitutes an important drug target. We captured the dengue virus NS3 helicase at several stages along the catalytic pathway including bound to single-stranded (ss) RNA, to an ATP analogue, to a transition-state analogue and to ATP hydrolysis products. RNA recognition appears largely sequence independent in a way remarkably similar to eukaryotic DEAD box proteins Vasa and eIF4AIII. On ssRNA binding, the NS3 enzyme switches to a catalytic-competent state imparted by an inward movement of the P-loop, interdomain closure and a change in the divalent metal coordination shell, providing a structural basis for RNA-stimulated ATP hydrolysis. These structures demonstrate for the first time large quaternary changes in the flaviviridae helicase, identify the catalytic water molecule and point to a beta-hairpin that protrudes from subdomain 2, as a critical element for dsRNA unwinding. They also suggest how NS3 could exert an effect as an RNA-anchoring device and thus participate both in flavivirus RNA replication and assembly. | |||
Insights into RNA unwinding and ATP hydrolysis by the flavivirus NS3 protein.,Luo D, Xu T, Watson RP, Scherer-Becker D, Sampath A, Jahnke W, Yeong SS, Wang CH, Lim SP, Strongin A, Vasudevan SG, Lescar J EMBO J. 2008 Dec 3;27(23):3209-19. Epub 2008 Nov 13. PMID:19008861<ref>PMID:19008861</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2jlv" style="background-color:#fffaf0;"></div> | |||
== | |||
==See Also== | ==See Also== | ||
*[[Helicase]] | *[[Helicase 3D structures|Helicase 3D structures]] | ||
*[[Virus protease 3D structures|Virus protease 3D structures]] | |||
== | == References == | ||
< | <references/> | ||
[[Category: Dengue virus 4]] | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Becker | [[Category: Dengue virus 4 Thailand/0348/1991]] | ||
[[Category: Jahnke | [[Category: Large Structures]] | ||
[[Category: Lescar | [[Category: Becker DS]] | ||
[[Category: Lim | [[Category: Jahnke W]] | ||
[[Category: Luo | [[Category: Lescar J]] | ||
[[Category: Sampath | [[Category: Lim SP]] | ||
[[Category: Vasudevan | [[Category: Luo DH]] | ||
[[Category: Wang | [[Category: Sampath A]] | ||
[[Category: Watson | [[Category: Vasudevan SG]] | ||
[[Category: Xu | [[Category: Wang CH]] | ||
[[Category: Yeong | [[Category: Watson RP]] | ||
[[Category: Xu T]] | |||
[[Category: Yeong SS]] | |||