6OQ6

Structure of the pore forming fragment of Clostridium difficile toxin B in complex with VHH 5D

Summary for 6OQ6

• Entry DOI: 10.2210/pdb6oq6/pdb
• Descriptor: Toxin B, 5D (2 entities in total)
• Functional Keywords: toxin vhh, toxin
• Biological source: Clostridioides difficile; More
• Total number of polymer chains: 2
• Total formula weight: 57405.43

Authors

Chen, P.,Lam, K.,Jin, R. (deposition date: 2019-04-25, release date: 2019-07-10, Last modification date: 2024-10-30)

Primary citation

Chen, P.,Lam, K.H.,Liu, Z.,Mindlin, F.A.,Chen, B.,Gutierrez, C.B.,Huang, L.,Zhang, Y.,Hamza, T.,Feng, H.,Matsui, T.,Bowen, M.E.,Perry, K.,Jin, R.
Structure of the full-length Clostridium difficile toxin B.
Nat.Struct.Mol.Biol., 26:712-719, 2019

PubMed Abstract: 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.

PubMed: 31308519
DOI: 10.1038/s41594-019-0268-0

Experimental method

X-RAY DIFFRACTION (2.97 Å)