6vx4

Density-fitted Model Structure of Antibody Variable Domains of TyTx11 in Complex with Typhoid Toxin

spinqualitylabelsall models 6vx4, resolution 3.12Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6vx4 is a 9 chain structure with sequence from Mus musculus and Salmonella enterica subsp. enterica serovar Typhi str. CT18. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.12Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Nearly all clinical isolates of Salmonella Typhi, the cause of typhoid fever, are antibiotic resistant. All S. Typhi isolates secrete an A(2)B(5) exotoxin called typhoid toxin to benefit the pathogen during infection. Here, we demonstrate that antibiotic-resistant S. Typhi secretes typhoid toxin continuously during infection regardless of antibiotic treatment. We characterize typhoid toxin antibodies targeting glycan-receptor-binding PltB or nuclease CdtB, which neutralize typhoid toxin in vitro and in vivo, as demonstrated by using typhoid toxin secreted by antibiotic-resistant S. Typhi during human cell infection and lethal dose typhoid toxin challenge to mice. TyTx11 generated in this study neutralizes typhoid toxin effectively, comparable to TyTx4 that binds to all PltB subunits available per holotoxin. Cryoelectron microscopy explains that the binding of TyTx11 to CdtB makes this subunit inactive through CdtB catalytic-site conformational change. The identified toxin-neutralizing epitopes are conserved across all S. Typhi clinical isolates, offering critical insights into typhoid toxin-neutralizing strategies. Mechanisms of typhoid toxin neutralization by antibodies targeting glycan receptor binding and nuclease subunits.,Ahn C, Yang YA, Neupane DP, Nguyen T, Richards AF, Sim JH, Mantis NJ, Song J iScience. 2021 Apr 20;24(5):102454. doi: 10.1016/j.isci.2021.102454. eCollection , 2021 May 21. PMID:34113815 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures

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