Crystal structure of receptor-binding C-terminal repeats from Clostridium difficile toxin A

• DOI: 10.1073/pnas.0506391102
• Publication Date: 2005-12-13T02:03:36Z
• Authors: Jason G. S. Ho; Antonio Greco; Maja Rupnik; Kenneth K.-S. Ng
• Keywords: Models, Molecular; 0303 health sciences; Clostridioides difficile; Bacterial Toxins; Molecular Sequence Data; Hydrogen Bonding; Crystallography, X-Ray; Protein Structure, Tertiary; 3. Good health; Enterotoxins; 03 medical and health sciences; Amino Acid Sequence; Protein Binding

Clostridium difficile is a major nosocomial pathogen that produces two large protein toxins [toxin A (TcdA) and toxin B (TcdB)] capable of disrupting intestinal epithelial cells. Both belong to the family clostridial cytotoxins, which are characterized by presence repetitive C-terminal domain (CRD). In TcdA, CRD composed 39 repeats responsible for binding cell surface carbohydrates. To understand molecular structural basis from C. , we have determined 1.85-Å resolution crystal structure 127-aa fragment C terminus CRD. This reveals β-solenoid fold containing five repeats, with each repeat consisting β-hairpin followed loop 7–10 residues in short (SRs) or 18 long (LRs). Adjacent pairs β-hairpins related other either 90° 120° screw–axis rotational relationships, depending on nature amino acids at key positions adjacent β-hairpins. Models complete CRDs suggest contains straight stretches three SRs punctuated kinks introduced single LR. These features provide framework understanding how cytotoxins bind surfaces approaches developing novel treatments -associated diseases blocking surfaces.