Practice question

Specificity cholera toxin exemplifies glycan protein recognition medical consequence and cell biology tool. Vibrio cholerae AB5 holotoxin comprises catalytic A1 subunit ADP ribosyltransferase and homopentameric B subunits each containing binding pocket pentasaccharide GM1 Gal beta1-3 GalNAc beta1-4 Neu5Ac alpha2-3 Gal beta1-4 Glc ceramide. Key hydrogen bonds terminal galactose sialic acid provide nanomolar affinity positioning toxin on lipid rafts enterocytes small intestine. Raft mediated endocytosis delivers toxin retrograde trans Golgi ER where A1 ADP ribosylates Gs alpha arginine two hundred one locking GTP bound stimulating adenylate cyclase constitutively raising cAMP hundred fold opening CFTR chloride channels causing profuse watery diarrhea cholera gravis. Glucosylceramide lacks terminal sugars fails binding sulfatide distinct structure. GM1 knockout mice resist toxin GM1 supplemented liposomes detoxify pathogen. Interaction utilized neuronal tracing cholera toxin B HRP conjugates retrograde labeling dorsal root ganglia illustrating how glycolipid receptors dictate pathogenesis ABO blood group related susceptibility and toxin based tools for neuroscience and cell biology laboratory techniques widely taught in examinations.