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TitleTFPI is a colonic crypt receptor for TcdB from hypervirulent clade 2 C. difficile.
Journal, issue, pagesCell, Vol. 185, Issue 6, Page 980-994.e15, Year 2022
Publish dateMar 17, 2022
AuthorsJianhua Luo / Qi Yang / Xiaofeng Zhang / Yuanyuan Zhang / Li Wan / Xiechao Zhan / Yao Zhou / Liuqing He / Danyang Li / Dazhi Jin / Ying Zhen / Jing Huang / Yanyan Li / Liang Tao /
PubMed AbstractThe 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, ...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.
External linksCell / PubMed:35303428
MethodsEM (single particle)
Resolution3.2 - 3.7 Å
Structure data

31628

7v1n

EMDB-31628, PDB-7v1n:
Structure of the Clade 2 C. difficile TcdB in complex with its receptor TFPI
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-31629: Structure of the TFPI-TcdB4 complex
Method: EM (single particle) / Resolution: 3.7 Å

Source
  • clostridioides difficile (bacteria)
  • homo sapiens (human)
KeywordsTOXIN / TcdB4 / TFPI / receptor / complex

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