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The Shiga toxin 2a (Stx2a) B subunit is the receptor-binding component of the AB5 holotoxin produced by Shiga toxin-producing Escherichia coli (STEC) (UniProt P09385). It forms a homopentameric ring that specifically targets globotriaosylceramide (Gb3) receptors on the surface of host cells, particularly endothelial cells in the renal vasculature and central nervous system (Melton-Celsa, 2014). Once bound, the B subunit facilitates the internalization of the entire toxin complex via retrograde transport through the Golgi apparatus and endoplasmic reticulum (Johannes & Römer, 2010). This process is essential for the catalytic A subunit to reach the cytoplasm, where it halts protein synthesis and induces apoptosis. Stx2a is the variant most frequently associated with severe clinical outcomes, including Hemolytic Uremic Syndrome (HUS) (StatPearls, 2023). Therapeutic interventions targeting the B subunit, such as monoclonal antibodies like Urtoxazumab, aim to neutralize the toxin by preventing its attachment to host cells (Lopez et al., 2010). These treatments are designed to mitigate systemic damage during the early stages of infection before irreversible organ failure occurs.
Neutralization of the toxin by competitively inhibiting the binding of the B subunit pentamer to the host cell receptor globotriaosylceramide (Gb3), thereby preventing toxin internalization and subsequent cellular damage (Lopez et al., 2010).
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