8QEN
cryo-EM structure of apo Clostridioides difficile toxin B
Summary for 8QEN
| Entry DOI | 10.2210/pdb8qen/pdb |
| EMDB information | 18373 |
| Descriptor | Toxin B, ZINC ION (2 entities in total) |
| Functional Keywords | microbiology, pore forming region, crop dynamics, toxin, structural genomics, structural genomics consortium, sgc |
| Biological source | Clostridioides difficile |
| Total number of polymer chains | 1 |
| Total formula weight | 273616.97 |
| Authors | Kinsolving, J.,Bous, J.,Structural Genomics Consortium (SGC) (deposition date: 2023-09-01, release date: 2024-03-20) |
| Primary citation | Kinsolving, J.,Bous, J.,Kozielewicz, P.,Kosenina, S.,Shekhani, R.,Gratz, L.,Masuyer, G.,Wang, Y.,Stenmark, P.,Dong, M.,Schulte, G. Structural and functional insight into the interaction of Clostridioides difficile toxin B and FZD 7. Cell Rep, 43:113727-113727, 2024 Cited by PubMed Abstract: The G protein-coupled receptors of the Frizzled (FZD) family, in particular FZD, are receptors that are exploited by Clostridioides difficile toxin B (TcdB), the major virulence factor responsible for pathogenesis associated with Clostridioides difficile infection. We employ a live-cell assay examining the affinity between full-length FZDs and TcdB. Moreover, we present cryoelectron microscopy structures of TcdB alone and in complex with full-length FZD, which reveal that large structural rearrangements of the combined repetitive polypeptide domain are required for interaction with FZDs and other TcdB receptors, constituting a first step for receptor recognition. Furthermore, we show that bezlotoxumab, an FDA-approved monoclonal antibody to treat Clostridioides difficile infection, favors the apo-TcdB structure and thus disrupts binding with FZD. The dynamic transition between the two conformations of TcdB also governs the stability of the pore-forming region. Thus, our work provides structural and functional insight into how conformational dynamics of TcdB determine receptor binding. PubMed: 38308843DOI: 10.1016/j.celrep.2024.113727 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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