4uif

Cryo-EM structure of Dengue virus serotype 2 in complex with antigen-binding fragments of human antibody 2D22

Loading... Status: waiting for Mol* initialization Structural highlights 4uif is a 12 chain structure with sequence from Dengue virus 2 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 6.5Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function E0WXJ2_9FLAV Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune response.[ARBA:ARBA00024317] Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[ARBA:ARBA00003504] Serine protease subunit NS2B: Required cofactor for the serine protease function of NS3.[PROSITE-ProRule:PRU00859] Publication Abstract from PubMed There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics. DENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers.,Fibriansah G, Ibarra KD, Ng TS, Smith SA, Tan JL, Lim XN, Ooi JS, Kostyuchenko VA, Wang J, de Silva AM, Harris E, Crowe JE Jr, Lok SM Science. 2015 Jul 3;349(6243):88-91. doi: 10.1126/science.aaa8651. PMID:26138979 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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