Clostridioides difficile Toxin A receptor-binding domain (TcdA-RBD)

The Clostridioides difficile Toxin A (TcdA) receptor-binding domain is a critical structural component of the TcdA exotoxin, primarily responsible for the initial attachment of the toxin to the intestinal epithelium. This domain, located at the C-terminus of the protein, is characterized by multiple repetitive sequences known as Combined Repetitive Oligopeptides (CROPs) that adopt a beta-solenoid fold to facilitate multivalent binding to carbohydrate receptors on host cell membranes (UniProt P16154; PMID: 16243311). Following binding, the toxin is internalized via receptor-mediated endocytosis, leading to the delivery of an effector glucosyltransferase domain into the cytosol, which inactivates Rho-family GTPases and causes massive cytoskeletal disruption and cell death (PMID: 21810451). Because this domain is essential for toxin entry, it serves as a primary target for therapeutic interventions, such as neutralizing monoclonal antibodies. For instance, the human monoclonal antibody actoxumab was developed to bind specifically to this domain, neutralizing the toxin's ability to interact with host cells and thereby preventing the inflammatory damage associated with Clostridioides difficile infection (PMID: 28125351). Targeting the RBD is a key strategy in passive immunization to reduce the severity and recurrence of colitis in infected patients.

Other names

TcdA CROPs domainToxin A C-terminal domainClostridium difficile Toxin ATcdACombined Repetitive Oligopeptides domain

Neutralization of toxin activity by blocking the interaction between the receptor-binding domain and host cell surface receptors, thereby preventing toxin internalization and subsequent cytopathic effects.