View source for 4ffz


==Crystal Structure of DENV1-E111 fab fragment bound to DENV-1 DIII (Western Pacific-74 strain).==
<StructureSection load='4ffz' size='340' side='right'caption='[[4ffz]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ffz]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_1_Nauru/West_Pac/1974 Dengue virus 1 Nauru/West Pac/1974] 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=4FFZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FFZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.8&#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=4ffz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ffz OCA], [https://pdbe.org/4ffz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ffz RCSB], [https://www.ebi.ac.uk/pdbsum/4ffz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ffz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q88640_9FLAV Q88640_9FLAV] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We previously developed a panel of neutralizing monoclonal antibodies against Dengue virus (DENV)-1, of which few exhibited inhibitory activity against all DENV-1 genotypes. This finding is consistent with reports observing variable neutralization of different DENV strains and genotypes using serum from individuals that experienced natural infection or immunization. Herein, we describe the crystal structures of DENV1-E111 bound to a novel CC' loop epitope on domain III (DIII) of the E protein from two different DENV-1 genotypes. Docking of our structure onto the available cryo-electron microscopy models of DENV virions revealed that the DENV1-E111 epitope was inaccessible, suggesting that this antibody recognizes an uncharacterized virus conformation. While the affinity of binding between DENV1-E111 and DIII varied by genotype, we observed limited correlation with inhibitory activity. Instead, our results support the conclusion that potent neutralization depends on genotype-dependent exposure of the CC' loop epitope. These findings establish new structural complexity of the DENV virion, which may be relevant for the choice of DENV strain for induction or analysis of neutralizing antibodies in the context of vaccine development.

Structural Basis of Differential Neutralization of DENV-1 Genotypes by an Antibody that Recognizes a Cryptic Epitope.,Austin SK, Dowd KA, Shrestha B, Nelson CA, Edeling MA, Johnson S, Pierson TC, Diamond MS, Fremont DH PLoS Pathog. 2012 Oct;8(10):e1002930. doi: 10.1371/journal.ppat.1002930. Epub, 2012 Oct 4. PMID:23055922<ref>PMID:23055922</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ffz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dengue virus 1 Nauru/West Pac/1974]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Austin SK]]
[[Category: Fremont DH]]
[[Category: Nelson CA]]