Nature structural & molecular biology, 2019-08, Vol.26 (8), p.712-719
2019
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- Autor(en) / Beteiligte
- Titel
- Structure of the full-length Clostridium difficile toxin B
- Ist Teil von
- Nature structural & molecular biology, 2019-08, Vol.26 (8), p.712-719
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Clostridium difficile is an opportunistic pathogen that establishes in the colon when the gut microbiota are disrupted by antibiotics or disease. C. difficile infection (CDI) is largely caused by two virulence factors, TcdA and TcdB. Here, we report a 3.87-Å-resolution crystal structure of TcdB holotoxin that captures a unique conformation of TcdB at endosomal pH. Complementary biophysical studies suggest that the C-terminal combined repetitive oligopeptides (CROPs) domain of TcdB is dynamic and can sample open and closed conformations that may facilitate modulation of TcdB activity in response to environmental and cellular cues during intoxication. Furthermore, we report three crystal structures of TcdB-antibody complexes that reveal how antibodies could specifically inhibit the activities of individual TcdB domains. Our studies provide novel insight into the structure and function of TcdB holotoxin and identify intrinsic vulnerabilities that could be exploited to develop new therapeutics and vaccines for the treatment of CDI.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1545-9993eISSN: 1545-9985DOI: 10.1038/s41594-019-0268-0Titel-ID: cdi_pubmed_primary_31308519
- Format
- –
- Schlagworte
- Amino Acid Sequence, Antibodies, Neutralizing - immunology, Antigen-Antibody Complex - chemistry, Bacterial Proteins - chemistry, Bacterial Proteins - immunology, Bacterial Toxins - chemistry, Bacterial Toxins - immunology, Clostridioides difficile - chemistry, Conserved Sequence, Crystallography, X-Ray, Endosomes - chemistry, Hydrogen-Ion Concentration, Hydrophobic and Hydrophilic Interactions, Liposomes, Membrane Potentials, Models, Molecular, Peptide Fragments - chemistry, Protein Binding, Protein Conformation, Sequence Alignment, Sequence Homology, Amino Acid