Structural Basis for Recognition of Frizzled Proteins by Toxin B

Overview

Journal Science

Specialty Science

Date 2018 May 12

PMID 29748286

Citations 77

Authors

Peng Chen

Liang Tao

Tianyu Wang

Jie Zhang

Aina He

Kwok-Ho Lam

Zheng Liu

Xi He

Kay Perry

Min Dong

Rongsheng Jin

Affiliations

Soon will be listed here.

Abstract

infection is the most common cause of antibiotic-associated diarrhea in developed countries. The major virulence factor, 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.

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