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3c6r
From Proteopedia
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==Low pH Immature Dengue Virus== | ==Low pH Immature Dengue Virus== | ||
| - | < | + | <SX load='3c6r' size='340' side='right' viewer='molstar' caption='[[3c6r]], [[Resolution|resolution]] 25.00Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3c6r]] is a 6 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[3c6r]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_2_Thailand/PUO-218/1980 Dengue virus 2 Thailand/PUO-218/1980]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C6R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C6R FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 25Å</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=3c6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c6r OCA], [https://pdbe.org/3c6r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c6r RCSB], [https://www.ebi.ac.uk/pdbsum/3c6r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c6r ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/POLG_DEN2U POLG_DEN2U] 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). |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c6/3c6r_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c6/3c6r_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | + | </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=3c6r ConSurf]. |
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Intracellular cleavage of immature flaviviruses is a critical step in assembly that generates the membrane fusion potential of the E glycoprotein. With cryo-electron microscopy we show that the immature dengue particles undergo a reversible conformational change at low pH that renders them accessible to furin cleavage. At a pH of 6.0, the E proteins are arranged in a herringbone pattern with the pr peptides docked onto the fusion loops, a configuration similar to that of the mature virion. After cleavage, the dissociation of pr is pH-dependent, suggesting that in the acidic environment of the trans-Golgi network pr is retained on the virion to prevent membrane fusion. These results suggest a mechanism by which flaviviruses are processed and stabilized in the host cell secretory pathway. | ||
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| - | Structure of the immature dengue virus at low pH primes proteolytic maturation.,Yu IM, Zhang W, Holdaway HA, Li L, Kostyuchenko VA, Chipman PR, Kuhn RJ, Rossmann MG, Chen J Science. 2008 Mar 28;319(5871):1834-7. PMID:18369148<ref>PMID:18369148</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
| - | </ | + | </SX> |
| - | [[Category: Dengue virus 2 | + | [[Category: Dengue virus 2 Thailand/PUO-218/1980]] |
| - | [[Category: Chen | + | [[Category: Large Structures]] |
| - | [[Category: Chipman | + | [[Category: Chen J]] |
| - | [[Category: Holdway | + | [[Category: Chipman PR]] |
| - | [[Category: Kostyuchenko | + | [[Category: Holdway HA]] |
| - | [[Category: Kuhn | + | [[Category: Kostyuchenko VA]] |
| - | [[Category: Li | + | [[Category: Kuhn RJ]] |
| - | [[Category: Rossmann | + | [[Category: Li L]] |
| - | [[Category: Yu | + | [[Category: Rossmann MG]] |
| - | [[Category: Zhang | + | [[Category: Yu I]] |
| - | + | [[Category: Zhang W]] | |
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Current revision
Low pH Immature Dengue Virus
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