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Zalem, D;JuhÃ¡s, M;Terrinoni, M;King-Lyons, N;Lebens, M;Varrot, A;Connell, TD;Teneberg, S;
The heat-labile enterotoxins of Escherichia coli and cholera toxin of Vibrio cholerae are related in structure and function. Each of these oligomeric toxins are comprised of one A polypeptide and five B polypeptides. The B-subunits bind to gangliosides, which is followed by uptake into the intoxicated cell and activation of the host’s adenylate cyclase by the A-subunits. There are two antigenically distinct groups of these toxins. Group I includes cholera toxin and type I heat-labile enterotoxin of E. coli; group II contains the type II heat-labile enterotoxins of E. coli. Three variants of type II toxins, designated LT-IIa, LT-IIb and LT-IIc have been described. Earlier studies revealed the crystalline structure of LT-IIb. Herein the carbohydrate binding specificity of LT-IIc B-subunits was investigated by glycosphingolipid binding studies on thin-layer chromatograms and in microtiter wells. Binding studies using a large variety of glycosphingolipids showed that LT-IIc binds with high affinity to gangliosides with a terminal Neu5Ac〈3Gal or Neu5Gc〈3Gal sequence, e.g. the gangliosides GM3, GD1a and Neu5Ac〈3-/Neu5Gc〈3-neolactotetraosylceramide and Neu5Ac〈3-/Neu5Gc〈3-neolactohexaosylceramide. The crystal structure of LT-IIc B-subunits alone and with bound LSTd/sialyl-lacto-N-neotetraose d pentasaccharide uncovered the molecular basis of the ganglioside recognition. These studies revealed common and unique functional structures of the type II family of heat-labile enterotoxins.