6VX4
Density-fitted Model Structure of Antibody Variable Domains of TyTx11 in Complex with Typhoid Toxin
Summary for 6VX4
| Entry DOI | 10.2210/pdb6vx4/pdb |
| EMDB information | 21429 |
| Descriptor | Variable Domain of Kappa Chain of TyTx11 Antibody, Pertussis like toxin subunit B, Variable Domain of Heavy Chain of Antibody TyTx11, ... (5 entities in total) |
| Functional Keywords | typhoid toxin, a2b5, antibody, fab, toxin |
| Biological source | Mus musculus (Mouse) More |
| Total number of polymer chains | 9 |
| Total formula weight | 147821.79 |
| Authors | Nguyen, T.,Song, J. (deposition date: 2020-02-21, release date: 2021-02-24, Last modification date: 2024-11-13) |
| Primary citation | Ahn, C.,Yang, Y.A.,Neupane, D.P.,Nguyen, T.,Richards, A.F.,Sim, J.H.,Mantis, N.J.,Song, J. Mechanisms of typhoid toxin neutralization by antibodies targeting glycan receptor binding and nuclease subunits. Iscience, 24:102454-102454, 2021 Cited by PubMed Abstract: Nearly all clinical isolates of Typhi, the cause of typhoid fever, are antibiotic resistant. All Typhi isolates secrete an AB exotoxin called typhoid toxin to benefit the pathogen during infection. Here, we demonstrate that antibiotic-resistant 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 and , as demonstrated by using typhoid toxin secreted by antibiotic-resistant 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 Typhi clinical isolates, offering critical insights into typhoid toxin-neutralizing strategies. PubMed: 34113815DOI: 10.1016/j.isci.2021.102454 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.12 Å) |
Structure validation
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