Year: 2018
Type: article
Abstract: Toxic hijack of a cell signaling pathway The pathogen Clostridium difficile colonizes the human colon when the normal microbiota is disrupted, often after antibiotic treatment. It is a leading cause of hospital-acquired diarrhea, especially among elderly patients. Chen et al. describe a 2.5-Å-resolution crystal structure that shows how a major virulence factor in C. difficile , toxin B (TcdB), binds to the G protein–coupled receptor Frizzled (FZD). This receptor activates the Wnt signaling pathway, which regulates homeostasis of the colonic epithelium. Surprisingly, TcdB uses a lipid cofactor to recognize FZD. This cofactor replaces a lipid normally associated with the Wnt ligand that binds FZD to activate signaling. Inhibiting the Wnt pathway likely plays a role in C. difficile pathology. Science , this issue p. 664
Source: Science
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1030164648, G117057553, G1633935697, G16932012, G2921133296, G4216773172, G4301170177, Structural mechanism for recognition of host receptor by botulinum neurotoxin A, G487844314, G5384392517, G8158403594, G8498698609, Intellectual and Developmental Disablities Research Center, Integrated Epithelial and Muscosal Biology
OpenAlex ID: W2800005259