7V1N

Structure of the Clade 2 C. difficile TcdB in complex with its receptor TFPI

Summary for 7V1N

• Entry DOI: 10.2210/pdb7v1n/pdb
• EMDB information: 31628
• Descriptor: Toxin B, Isoform Beta of Tissue factor pathway inhibitor (2 entities in total)
• Functional Keywords: tcdb4, tfpi, receptor, complex, toxin
• Biological source: Clostridioides difficile (Peptoclostridium difficile); More
• Total number of polymer chains: 2
• Total formula weight: 299135.63

Authors

Luo, J.,Yang, Q.,Zhang, X.,Zhang, Y.,Wan, L.,Li, Y.,Tao, L. (deposition date: 2021-08-05, release date: 2022-02-23, Last modification date: 2024-10-30)

Primary citation

Luo, J.,Yang, Q.,Zhang, X.,Zhang, Y.,Wan, L.,Zhan, X.,Zhou, Y.,He, L.,Li, D.,Jin, D.,Zhen, Y.,Huang, J.,Li, Y.,Tao, L.
TFPI is a colonic crypt receptor for TcdB from hypervirulent clade 2 C. difficile.
Cell, 185:980-994.e15, 2022

PubMed Abstract: The emergence of hypervirulent clade 2 Clostridioides difficile is associated with severe symptoms and accounts for >20% of global infections. TcdB is a dominant virulence factor of C. difficile, and clade 2 strains exclusively express two TcdB variants (TcdB2 and TcdB4) that use unknown receptors distinct from the classic TcdB. Here, we performed CRISPR/Cas9 screens for TcdB4 and identified tissue factor pathway inhibitor (TFPI) as its receptor. Using cryo-EM, we determined a complex structure of the full-length TcdB4 with TFPI, defining a common receptor-binding region for TcdB. Residue variations within this region divide major TcdB variants into 2 classes: one recognizes Frizzled (FZD), and the other recognizes TFPI. TFPI is highly expressed in the intestinal glands, and recombinant TFPI protects the colonic epithelium from TcdB2/4. These findings establish TFPI as a colonic crypt receptor for TcdB from clade 2 C. difficile and reveal new mechanisms for CDI pathogenesis.

PubMed: 35303428
DOI: 10.1016/j.cell.2022.02.010

Experimental method

ELECTRON MICROSCOPY (3.2 Å)