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| | ==Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody== | | ==Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody== |
| - | <StructureSection load='3j42' size='340' side='right' caption='[[3j42]], [[Resolution|resolution]] 21.00Å' scene=''> | + | <SX load='3j42' size='340' side='right' viewer='molstar' caption='[[3j42]], [[Resolution|resolution]] 21.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3j42]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_2 Dengue virus 2] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J42 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3J42 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3j42]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_2 Dengue virus 2] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J42 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3J42 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3c6d|3c6d]], [[4kvc|4kvc]]</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]] 21Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Igh-1a, Igh ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Gm16939 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3j42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j42 OCA], [https://pdbe.org/3j42 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3j42 RCSB], [https://www.ebi.ac.uk/pdbsum/3j42 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3j42 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3j42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j42 OCA], [http://pdbe.org/3j42 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3j42 RCSB], [http://www.ebi.ac.uk/pdbsum/3j42 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3j42 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/O11875_9FLAV O11875_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] [[http://www.uniprot.org/uniprot/Q3BCY5_9FLAV Q3BCY5_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] | + | [https://www.uniprot.org/uniprot/O11875_9FLAV O11875_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] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| | [[Category: Dengue virus 2]] | | [[Category: Dengue virus 2]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Jiang, W]] | + | [[Category: Mus musculus]] |
| - | [[Category: Pennington, J G]] | + | [[Category: Jiang W]] |
| - | [[Category: Rossmann, M G]] | + | [[Category: Pennington JG]] |
| - | [[Category: Wang, Z]] | + | [[Category: Rossmann MG]] |
| - | [[Category: Antibody]] | + | [[Category: Wang Z]] |
| - | [[Category: Dengue]]
| + | |
| - | [[Category: Immature]]
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| - | [[Category: Maturation]]
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| - | [[Category: Virus-immune system complex]]
| + | |
| Structural highlights
Function
O11875_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]
Publication Abstract from PubMed
The 2H2 monoclonal antibody recognizes the precursor peptide on the immature dengue virus and might, therefore, be a useful tool for investigating the conformational change that occurs when the immature virus enters an acidic environment. During dengue virus maturation, the spiky, immature, non-infectious virions change their structure to smooth-surfaced particles in the slightly acid environment of the trans-Golgi network, thereby allowing cellular furin to cleave the precursor-membrane proteins. The dengue virions become fully infectious when they release the cleaved precursor peptide on reaching the neutral pH environment of the extracellular space. Here we report on the cryo-electron microscopy structures of the immature virus complexed with the 2H2 antigen binding fragments (Fab) at different concentrations and varied pH conditions. At neutral pH and high concentration of the Fab molecules, three Fab molecules bind to three precursor-membrane proteins on each spike of the immature virus. However, at a low concentration of the Fab molecules and at pH 7.0, only two Fab molecules bind to each spike. Changing to slightly acidic pH caused no detectable change of structure for the high Fab concentration sample, but caused severe structural damage to the low concentration sample. Therefore, the 2H2 Fab inhibits the maturation process of immature dengue virus when the Fab molecules are at high concentration, because the three Fab molecules on each spike hold the precursor-membrane molecules together, thereby inhibiting the normal conformational change that occurs during maturation.
Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody.,Wang Z, Li L, Pennington JG, Sheng J, Yap ML, Plevka P, Meng G, Sun L, Jiang W, Rossmann MG J Virol. 2013 Jun 5. PMID:23740974[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang Z, Li L, Pennington JG, Sheng J, Yap ML, Plevka P, Meng G, Sun L, Jiang W, Rossmann MG. Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody. J Virol. 2013 Jun 5. PMID:23740974 doi:10.1128/JVI.00472-13
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