2r6p: Difference between revisions

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<SX load='2r6p' size='340' side='right' viewer='molstar' caption='[[2r6p]], [[Resolution|resolution]] 24.00&Aring;' scene=''>
<SX load='2r6p' size='340' side='right' viewer='molstar' caption='[[2r6p]], [[Resolution|resolution]] 24.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2r6p]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Den2p Den2p] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. The July 2008 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Dengue Virus''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2008_7 10.2210/rcsb_pdb/mom_2008_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R6P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R6P FirstGlance]. <br>
<table><tr><td colspan='2'>[[2r6p]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_2_Puerto_Rico/PR159-S1/1969 Dengue virus 2 Puerto Rico/PR159-S1/1969] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. The July 2008 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Dengue Virus''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2008_7 10.2210/rcsb_pdb/mom_2008_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R6P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R6P FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">E protein ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11066 DEN2P]), immunoglobulin ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 24&#8491;</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=2r6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r6p OCA], [https://pdbe.org/2r6p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r6p RCSB], [https://www.ebi.ac.uk/pdbsum/2r6p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r6p ProSAT]</span></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=2r6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r6p OCA], [https://pdbe.org/2r6p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r6p RCSB], [https://www.ebi.ac.uk/pdbsum/2r6p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r6p 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).
[https://www.uniprot.org/uniprot/Q66394_9FLAV Q66394_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:SAAS011998_004_099774]
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=2r6p ConSurf].
</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=2r6p ConSurf].
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== Publication Abstract from PubMed ==
The monoclonal antibody 1A1D-2 has been shown to strongly neutralize dengue virus serotypes 1, 2 and 3, primarily by inhibiting attachment to host cells. A crystal structure of its antigen binding fragment (Fab) complexed with domain III of the viral envelope glycoprotein, E, showed that the epitope would be partially occluded in the known structure of the mature dengue virus. Nevertheless, antibody could bind to the virus at 37 degrees C, suggesting that the virus is in dynamic motion making hidden epitopes briefly available. A cryo-electron microscope image reconstruction of the virus:Fab complex showed large changes in the organization of the E protein that exposed the epitopes on two of the three E molecules in each of the 60 icosahedral asymmetric units of the virus. The changes in the structure of the viral surface are presumably responsible for inhibiting attachment to cells.
Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins.,Lok SM, Kostyuchenko V, Nybakken GE, Holdaway HA, Battisti AJ, Sukupolvi-Petty S, Sedlak D, Fremont DH, Chipman PR, Roehrig JT, Diamond MS, Kuhn RJ, Rossmann MG Nat Struct Mol Biol. 2008 Mar;15(3):312-7. Epub 2008 Feb 10. PMID:18264114<ref>PMID:18264114</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 2r6p" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</SX>
</SX>
[[Category: Den2p]]
[[Category: Dengue Virus]]
[[Category: Dengue Virus]]
[[Category: Dengue virus 2 Puerto Rico/PR159-S1/1969]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Mus musculus]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Chipman, P R]]
[[Category: Chipman PR]]
[[Category: Holdaway, H A]]
[[Category: Holdaway HA]]
[[Category: Kostyuchenko, V K]]
[[Category: Kostyuchenko VK]]
[[Category: Kuhn, R J]]
[[Category: Kuhn RJ]]
[[Category: Lok, S M]]
[[Category: Lok SM]]
[[Category: Rossmann, M G]]
[[Category: Rossmann MG]]
[[Category: Dengue]]
[[Category: Fab]]
[[Category: Icosahedral virus]]
[[Category: Neutralization]]
[[Category: Virus]]
[[Category: Virus-immune system complex]]
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