Common architecture of the primary galactose binding sites of Erythrina corallodendron lectin and heat-labile enterotoxin from Escherichia coli in relation to the binding of branched neolactohexaosylceramide

The heat-labile enterotoxin from Escherichia coli (LT) is responsible for s o-called traveller's diarrhea and is closely related to the cholera toxin ( CT), Toxin binding to GM1 at the epithelial cell surface of the small intes tine initiates the subsequent diarrheal disease. However, LT has a broader receptor specificity than CT in that it also binds to N-acetyllactosamine-t erminated structures. The unrelated lectin from Erythrina corallodendron (E CorL) shares this latter binding property, The findings that both ECorL and porcine LT (pLT) bind to lactose as well as to neolactotetraosylceramide s uggests a common structural theme in their respective primary binding sites . Superimposing the terminal galactose of the lactoses in the respective cr ystal structures of pLT and ECorL reveals striking structural similarities around the galactose despite the lack of sequence and folding homology, whe reas the interactions of the penultimate GlcNAc beta 3 in the neolactotetra osylceramide differ. The binding of branched neolactohexaosylceramide to ei ther protein reveals an enhanced affinity relative to neolactotetraosylcera mide. The beta 3-linked branch is found to bind to the primary Gal binding pocket of both proteins, whereas the beta 6-linked branch outside this site provides additional interactions in accordance with the higher binding aff inities found for this compound. While the remarkable architectural similar ities of the primary galactose binding sites of pLT and ECorL point to a co nvergent evolution of these subsites, the distinguishing structural feature s determining the overall carbohydrate specificities are located in extende d binding site regions. In pLT, Arg13 is thus found to play a crucial role in. enhancing the affinity not only for N-acetyllactosamine-terminated stru ctures but also for GM1 as compared to human LT (hLT) and CT. The physiolog ical relevance of the binding of N-acetyllactosamine-containing glycoconjug ates to LT and ECorL is briefly discussed.