Structural insight into Wnt signaling inhibition by Clostridium difficile toxin B

FEBS J. 2019 Mar;286(5):874-881. doi: 10.1111/febs.14681. Epub 2018 Nov 1.

Abstract

The incidence of Clostridium difficile infection (CDI) has increased significantly worldwide, causing substantial morbidity and mortality. One of the major virulence factor, TcdB, manages to enter the colonic epithelia via the human frizzled proteins (FZDs), which are physiological receptors for Wnt morphogens. Binding of TcdB to FZDs inhibits Wnt signaling, which may contribute to pathogenesis of CDI. Here, we review the structural mechanism by which TcdB exploits to recognize FZDs for cell entry and inhibiting Wnt signaling, which reveals new strategies to modulate Wnt signaling for therapeutic interventions.

Keywords: Clostridium difficile; Clostridium difficile infection; Wnt signaling; bacterial toxin; cancers; frizzled; host-pathogen interactions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / pharmacology*
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / pharmacology*
  • Binding Sites
  • Dimerization
  • Enterotoxins / chemistry
  • Enterotoxins / pharmacology*
  • Frizzled Receptors / metabolism
  • Protein Conformation
  • Signal Transduction
  • Structure-Activity Relationship
  • Wnt Signaling Pathway / drug effects*

Substances

  • Bacterial Proteins
  • Bacterial Toxins
  • Enterotoxins
  • Frizzled Receptors
  • toxB protein, Clostridium difficile