4ffz

Crystal Structure of DENV1-E111 fab fragment bound to DENV-1 DIII (Western Pacific-74 strain).

spinqualitylabelsall models 4ffz, resolution 3.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ffz is a 6 chain structure with sequence from Dengue virus 1 Nauru/West Pac/1974 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.8Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q88640_9FLAV 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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