5n09

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

spinqualitylabelsall models 5n09, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5n09 is a 6 chain structure with sequence from Dengue virus 2 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BMA, NAG, FUC, MAN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [C3VXD1_9FLAV] Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[SAAS:SAAS00882589] 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures 3D structures of human antibody

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