3i50

Crystal structure of the West Nile Virus envelope glycoprotein in complex with the E53 antibody Fab

spinqualitylabelsall models 3i50, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3i50 is a 3 chain structure with sequence from Lk3 transgenic mice and Wnv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 2hg0, 2i69 Gene: ENVELOPE (WNV), Light chain of E53 antibody (LK3 transgenic mice), Heavy chain of E53 antibody (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Flaviviruses are a group of human pathogens causing severe encephalitic or hemorrhagic diseases that include West Nile, dengue and yellow fever viruses. Here, using X-ray crystallography we have defined the structure of the flavivirus cross-reactive antibody E53 that engages the highly conserved fusion loop of the West Nile virus envelope glycoprotein. Using cryo-electron microscopy, we also determined that E53 Fab binds preferentially to spikes in noninfectious, immature flavivirions but is unable to bind significantly to mature virions, consistent with the limited solvent exposure of the epitope. We conclude that the neutralizing impact of E53 and likely similar fusion-loop-specific antibodies depends on its binding to the frequently observed immature component of flavivirus particles. Our results elucidate how fusion-loop antibodies, which comprise a significant fraction of the humoral response against flaviviruses, can function to control infection without appreciably recognizing mature virions. As these highly cross-reactive antibodies are often weakly neutralizing they also may contribute to antibody-dependent enhancement and flavi virus pathogenesis thereby complicating development of safe and effective vaccines. Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody.,Cherrier MV, Kaufmann B, Nybakken GE, Lok SM, Warren JT, Chen BR, Nelson CA, Kostyuchenko VA, Holdaway HA, Chipman PR, Kuhn RJ, Diamond MS, Rossmann MG, Fremont DH EMBO J. 2009 Oct 21;28(20):3269-76. Epub 2009 Aug 27. PMID:19713934 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoclonal Antibodies 3D structures

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