4al8

From Proteopedia

(Difference between revisions)

Revision as of 06:10, 5 August 2016

Structure of Dengue virus DIII in complex with Fab 2H12

Structural highlights

4al8 is a 3 chain structure with sequence from Dengue virus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4ala, 4am0
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[Q8BE57_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

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Midgley CM, Flanagan A, Tran HB, Dejnirattisai W, Chawansuntati K, Jumnainsong A, Wongwiwat W, Duangchinda T, Mongkolsapaya J, Grimes JM, Screaton GR. Structural Analysis of a Dengue Cross-Reactive Antibody Complexed with Envelope Domain III Reveals the Molecular Basis of Cross-Reactivity. J Immunol. 2012 May 15;188(10):4971-9. Epub 2012 Apr 9. PMID:22491255 doi:10.4049/jimmunol.1200227

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4al8"

@@ Line 1: / Line 1: @@
 ==Structure of Dengue virus DIII in complex with Fab 2H12==
 <StructureSection load='4al8' size='340' side='right' caption='[[4al8]], [[Resolution|resolution]] 1.66&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ala|4ala]], [[4am0|4am0]]</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=4al8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4al8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4al8 RCSB], [http://www.ebi.ac.uk/pdbsum/4al8 PDBsum]</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=4al8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4al8 OCA], [http://pdbe.org/4al8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4al8 RCSB], [http://www.ebi.ac.uk/pdbsum/4al8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4al8 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4al8" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4al8

From Proteopedia

Revision as of 06:10, 5 August 2016

Structure of Dengue virus DIII in complex with Fab 2H12

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox