Structural basis for differential receptor binding of cholera and Escherichia coli heat-labile toxins: influence of heterologous amino acid substitutions in the cholera B-subunit

Molecular Microbiology
M BäckströmM Lebens

Abstract

The closely related B-subunits of cholera toxin (CTB) and Escherichia coli heat-labile enterotoxin (LTB) both bind strongly to GM1 ganglioside receptors but LTB can also bind to additional glycolipids and glycoproteins. A number of mutant CT B-subunits were generated by substituting CTB amino acids with those at the corresponding positions in LTB. These were used to investigate the influence of specific residues on receptor-binding specificity. A mutated CTB protein containing the first 25 residues of LTB in combination with LTB residues at positions 94 and 95, bound to the same extent as native LTB to both delipidized rabbit intestinal cell membranes, complex glycosphingolipids (polyglycosylceramides) and neolactotetraosylceramide, but not to non-GM1 intestinal glycosphingolipids. In contrast, when LTB amino acid substitutions in the 1-25 region were combined with those in the 75-83 region, a binding as strong as that of LTB to intestinal glycosphingolipids was observed. In addition, a mutant LTB with a single Gly-33-->Asp substitution that completely lacked affinity for both GM1 and non-GM1 glycosphingolipids could still bind to receptors in the intestinal cell membranes and to polyglycosylceramides. We conclude that the extr...Continue Reading

Citations

Mar 31, 1998·Journal of Immunological Methods·S LiljeqvistM Murby
Sep 26, 2008·Biochemical and Biophysical Research Communications·Pankaj V Alone, Lalit C Garg
Feb 10, 2019·International Journal of Molecular Sciences·Julie Elisabeth HeggelundUte Krengel
Jun 3, 2020·Nature Communications·Daniel RodererStefan Raunser
Aug 16, 2008·Carbohydrate Research·Haydn R SinclairRobert A Rastall

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