5n09: Difference between revisions
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==Crystal structure of L107C/A313C covalently linked dengue 2 virus envelope glycoprotein dimer in complex with the Fab fragment of the broadly neutralizing human antibody EDE2 A11== | |||
<StructureSection load='5n09' size='340' side='right' caption='[[5n09]], [[Resolution|resolution]] 3.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5n09]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_2 Dengue virus 2] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N09 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N09 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=5n09 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n09 OCA], [http://pdbe.org/5n09 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n09 RCSB], [http://www.ebi.ac.uk/pdbsum/5n09 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n09 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/C3VXD1_9FLAV C3VXD1_9FLAV]] Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[SAAS:SAAS00882589] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A problem in the search for an efficient vaccine against dengue virus is the immunodominance of the fusion loop epitope (FLE), a segment of the envelope protein E that is buried at the interface of the E dimers coating mature viral particles. Anti-FLE antibodies are broadly cross-reactive but poorly neutralizing, displaying a strong infection enhancing potential. FLE exposure takes place via dynamic 'breathing' of E dimers at the virion surface. In contrast, antibodies targeting the E dimer epitope (EDE), readily exposed at the E dimer interface over the region of the conserved fusion loop, are very potent and broadly neutralizing. We here engineer E dimers locked by inter-subunit disulfide bonds, and show by X-ray crystallography and by binding to a panel of human antibodies that these engineered dimers do not expose the FLE, while retaining the EDE exposure. These locked dimers are strong immunogen candidates for a next-generation vaccine. | |||
Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope.,Rouvinski A, Dejnirattisai W, Guardado-Calvo P, Vaney MC, Sharma A, Duquerroy S, Supasa P, Wongwiwat W, Haouz A, Barba-Spaeth G, Mongkolsapaya J, Rey FA, Screaton GR Nat Commun. 2017 May 23;8:15411. doi: 10.1038/ncomms15411. PMID:28534525<ref>PMID:28534525</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5n09" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Dengue virus 2]] | |||
[[Category: Human]] | |||
[[Category: Duquerroy, S]] | |||
[[Category: Guardado-Calvo, P]] | |||
[[Category: Rey, F]] | |||
[[Category: Rouvinski, A]] | [[Category: Rouvinski, A]] | ||
[[Category: Sharma, A]] | [[Category: Sharma, A]] | ||
[[Category: | [[Category: Vaney, M C]] | ||
[[Category: Broadly neutralizing antibody]] | |||
[[Category: Class 2 fusion protein]] | |||
[[Category: Dengue virus]] | |||
[[Category: Fab fragment]] | |||
[[Category: Immune system-viral protein complex]] | |||
[[Category: Membrane fusion]] | |||
[[Category: Viral protein]] | |||
Revision as of 10:48, 16 November 2017
Crystal structure of L107C/A313C covalently linked dengue 2 virus envelope glycoprotein dimer in complex with the Fab fragment of the broadly neutralizing human antibody EDE2 A11
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