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Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B

Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B

Peng Chen, Liang Tao, Tianyu Wang, Jie Zhang, Aina He, Kwok-Ho Lam, Zheng Liu, Xi He, Kay Perry, Min Dong, Rongsheng Jin

Science. 2018 May 11;360(6389):664-669.

PMID: 29748286

Abstract:

Clostridium difficile infection is the most common cause of antibiotic-associated diarrhea in developed countries. The major virulence factor, C. difficile toxin B (TcdB), targets colonic epithelia by binding to the frizzled (FZD) family of Wnt receptors, but how TcdB recognizes FZDs is unclear. Here, we present the crystal structure of a TcdB fragment in complex with the cysteine-rich domain of human FZD2 at 2.5-angstrom resolution, which reveals an endogenous FZD-bound fatty acid acting as a co-receptor for TcdB binding. This lipid occupies the binding site for Wnt-adducted palmitoleic acid in FZDs. TcdB binding locks the lipid in place, preventing Wnt from engaging FZDs and signaling. Our findings establish a central role of fatty acids in FZD-mediated TcdB pathogenesis and suggest strategies to modulate Wnt signaling.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4242912	Clostridium difficile Toxin B			Price

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