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[[ | ==Structure of Dengue virus DIII in complex with Fab 2H12== | ||
<StructureSection load='4ala' size='340' side='right' caption='[[4ala]], [[Resolution|resolution]] 1.84Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ala]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_3 Dengue virus 3] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ALA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ALA FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4al8|4al8]], [[4am0|4am0]]</td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ala FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ala OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ala RCSB], [http://www.ebi.ac.uk/pdbsum/4ala PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Dengue virus infections are still increasing at an alarming rate in tropical and subtropical countries, underlying the need for a dengue vaccine. Although it is relatively easy to generate Ab responses to dengue virus, low avidity or low concentrations of Ab may enhance infection of FcR-bearing cells with clinical impact, posing a challenge to vaccine production. In this article, we report the characterization of a mAb, 2H12, which is cross-reactive to all four serotypes in the dengue virus group. Crystal structures of 2H12-Fab in complex with domain III of the envelope protein from three dengue serotypes have been determined. 2H12 binds to the highly conserved AB loop of domain III of the envelope protein that is poorly accessible in the mature virion. 2H12 neutralization varied between dengue serotypes and strains; in particular, dengue serotype 2 was not neutralized. Because the 2H12-binding epitope was conserved, this variation in neutralization highlights differences between dengue serotypes and suggests that significant conformational changes in the virus must take place for Ab binding. Surprisingly, 2H12 facilitated little or no enhancement of infection. These data provide a structural basis for understanding Ab neutralization and enhancement of infection, which is crucial for the development of future dengue vaccines. | |||
Structural Analysis of a Dengue Cross-Reactive Antibody Complexed with Envelope Domain III Reveals the Molecular Basis of Cross-Reactivity.,Midgley CM, Flanagan A, Tran HB, Dejnirattisai W, Chawansuntati K, Jumnainsong A, Wongwiwat W, Duangchinda T, Mongkolsapaya J, Grimes JM, Screaton GR J Immunol. 2012 May 15;188(10):4971-9. Epub 2012 Apr 9. PMID:22491255<ref>PMID:22491255</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
< | |||
[[Category: Dengue virus 3]] | [[Category: Dengue virus 3]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
Revision as of 11:28, 5 June 2014
Structure of Dengue virus DIII in complex with Fab 2H12Structure of Dengue virus DIII in complex with Fab 2H12
Structural highlights
Publication Abstract from PubMedDengue virus infections are still increasing at an alarming rate in tropical and subtropical countries, underlying the need for a dengue vaccine. Although it is relatively easy to generate Ab responses to dengue virus, low avidity or low concentrations of Ab may enhance infection of FcR-bearing cells with clinical impact, posing a challenge to vaccine production. In this article, we report the characterization of a mAb, 2H12, which is cross-reactive to all four serotypes in the dengue virus group. Crystal structures of 2H12-Fab in complex with domain III of the envelope protein from three dengue serotypes have been determined. 2H12 binds to the highly conserved AB loop of domain III of the envelope protein that is poorly accessible in the mature virion. 2H12 neutralization varied between dengue serotypes and strains; in particular, dengue serotype 2 was not neutralized. Because the 2H12-binding epitope was conserved, this variation in neutralization highlights differences between dengue serotypes and suggests that significant conformational changes in the virus must take place for Ab binding. Surprisingly, 2H12 facilitated little or no enhancement of infection. These data provide a structural basis for understanding Ab neutralization and enhancement of infection, which is crucial for the development of future dengue vaccines. Structural Analysis of a Dengue Cross-Reactive Antibody Complexed with Envelope Domain III Reveals the Molecular Basis of Cross-Reactivity.,Midgley CM, Flanagan A, Tran HB, Dejnirattisai W, Chawansuntati K, Jumnainsong A, Wongwiwat W, Duangchinda T, Mongkolsapaya J, Grimes JM, Screaton GR J Immunol. 2012 May 15;188(10):4971-9. Epub 2012 Apr 9. PMID:22491255[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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