6OQ7

Structure of the GTD domain of Clostridium difficile toxin B in complex with VHH E3

6OQ7 の概要

• エントリーDOI: 10.2210/pdb6oq7/pdb
• 分子名称: Toxin B, E3, URIDINE-5'-DIPHOSPHATE, ... (7 entities in total)
• 機能のキーワード: toxin vhh, toxin
• 由来する生物種: Clostridioides difficile; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 78941.10

構造登録者

Chen, P.,Lam, K.,Jin, R. (登録日: 2019-04-25, 公開日: 2019-07-10, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.39 Å)