6C0B

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

6C0B の概要

• エントリーDOI: 10.2210/pdb6c0b/pdb
• 分子名称: Toxin B, Frizzled-2, MALONATE ION, ... (6 entities in total)
• 機能のキーワード: complex, toxin
• 由来する生物種: Clostridioides difficile (Peptoclostridium difficile); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77252.68

構造登録者

Chen, P.,Lam, K.,Jin, R. (登録日: 2017-12-28, 公開日: 2018-05-16, 最終更新日: 2024-11-06)

主引用文献

Chen, P.,Tao, L.,Wang, T.,Zhang, J.,He, A.,Lam, K.H.,Liu, Z.,He, X.,Perry, K.,Dong, M.,Jin, R.
Structural basis for recognition of frizzled proteins byClostridium difficiletoxin B.
Science, 360:664-669, 2018

PubMed 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.

PubMed: 29748286
DOI: 10.1126/science.aar1999

実験手法

X-RAY DIFFRACTION (2.5 Å)