6C0B

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

Summary for 6C0B

• Entry DOI: 10.2210/pdb6c0b/pdb
• Descriptor: Toxin B, Frizzled-2, MALONATE ION, ... (6 entities in total)
• Functional Keywords: complex, toxin
• Biological source: Clostridioides difficile (Peptoclostridium difficile); More
• Total number of polymer chains: 2
• Total formula weight: 77252.68

Authors

Chen, P.,Lam, K.,Jin, R. (deposition date: 2017-12-28, release date: 2018-05-16, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)