View source for 6kr3


==Crystal structure of Dengue virus nonstructural protein NS5 (form 2)==
<StructureSection load='6kr3' size='340' side='right'caption='[[6kr3]], [[Resolution|resolution]] 2.93&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6kr3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_2 Dengue virus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KR3 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]] 2.931&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6kr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kr3 OCA], [https://pdbe.org/6kr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kr3 RCSB], [https://www.ebi.ac.uk/pdbsum/6kr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kr3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q91H74_9FLAV Q91H74_9FLAV] 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).[SAAS:SAAS026470_004_099774]
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== Publication Abstract from PubMed ==
The flaviviruses pose serious threats to human health. Being a natural fusion of a methyltransferase (MTase) and an RNA-dependent RNA polymerase (RdRP), NS5 is the most conserved flavivirus protein and an important antiviral target. Previously reported NS5 structures represented by those from the Japanese encephalitis virus (JEV) and Dengue virus serotype 3 (DENV3) exhibit two apparently different global conformations, defining two sets of intra-molecular MTase-RdRP interactions. However, whether these NS5 conformations are conserved in flaviviruses and their specific functions remain elusive. Here we report two forms of DENV serotype 2 (DENV2) NS5 crystal structures representing two conformational states with defined analogies to the JEV-mode and DENV3-mode conformations, respectively, demonstrating the conservation of both conformation modes and providing clues for how different conformational states may be interconnected. Data from in vitro polymerase assays further demonstrate that perturbing the JEV-mode but not the DENV3-mode intra-molecular interactions inhibits catalysis only at initiation, while the cell-based virological analysis suggests that both modes of interactions are important for virus proliferation. Our work highlights the role of MTase as a unique intra-molecular initiation factor specifically only through the JEV-mode conformation, providing an example of conformation-based crosstalk between naturally fused protein functional modules.

A conformation-based intra-molecular initiation factor identified in the flavivirus RNA-dependent RNA polymerase.,Wu J, Ye HQ, Zhang QY, Lu G, Zhang B, Gong P PLoS Pathog. 2020 May 1;16(5):e1008484. doi: 10.1371/journal.ppat.1008484., eCollection 2020 May. PMID:32357182<ref>PMID:32357182</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6kr3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Dengue virus 2]]
[[Category: Large Structures]]
[[Category: Gong P]]
[[Category: Lu G]]
[[Category: Wu J]]
[[Category: Ye HQ]]