Comparison of the glycolipid-binding specificities of cholera toxin and porcine Escherichia coli heat-labile enterotoxin: identification of a receptor-active non-ganglioside glycolipid for the heat-labile toxin in infant rabbit small intestine

Glycoconj J. 1994 Dec;11(6):533-40. doi: 10.1007/BF00731304.

Abstract

The binding specificities of cholera toxin and Escherichia coli heat-labile enterotoxin were investigated by binding of 125I-labelled toxins to reference glycosphingolipids separated on thin-layer chromatograms and coated in microtitre wells. The binding of cholera toxin was restricted to the GM1 ganglioside. The heat-labile toxin showed the highest affinity for GM1 but also bound, though less strongly, to the GM2, GD2 and GD1b gangliosides and to the non-acid glycosphingolipids gangliotetraosylceramide and lactoneotetraosylceramide. The infant rabbit small intestine, a model system for diarrhoea induced by the toxins, was shown to contain two receptor-active glycosphingolipids for the heat-labile toxin, GM1 ganglioside and lactoneotetraosylceramide, whereas only the GM1 ganglioside was receptor-active for cholera toxin. Preliminary evidence was obtained, indicating that epithelial cells of human small intestine also contain lactoneotetraosylceramide and similar sequences. By computer-based molecular modelling, lactoneotetraosylceramide was docked into the active site of the heat-labile toxin, using the known crystal structure of the toxin in complex with lactose. Interactions which may explain the relatively high toxin affinity for this receptor were found.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins / metabolism*
  • Binding Sites
  • Carbohydrate Sequence
  • Cholera Toxin / metabolism*
  • Enterotoxins / metabolism*
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins*
  • G(M1) Ganglioside / metabolism
  • Glycosphingolipids / metabolism*
  • Intestine, Small / metabolism*
  • Molecular Sequence Data
  • Rabbits
  • Swine

Substances

  • Bacterial Toxins
  • Enterotoxins
  • Escherichia coli Proteins
  • Glycosphingolipids
  • heat-labile enterotoxin, E coli
  • G(M1) Ganglioside
  • Cholera Toxin