Comparison of the carbohydrate-binding specificities of cholera toxin and Escherichia coli heat-labile enterotoxins LTh-I, LT-IIa, and LT-IIb.
The heat-labile enterotoxins of Vibrio cholerae and Escherichia coli are related in structure and function. They are oligomers consisting of A and B polypeptide subunits. They bind to gangliosides, and they activate adenylate cyclase. The toxins form two antigenically distinct groups; members of each group cross-react but are not necessarily identical. Serogroup I includes cholera toxin (CT) and type I heat-labile enterotoxin (LT-I) of E. coli. LTh-I and LTp-I are antigenic variants of LT-I produced by strains of E. coli from humans and pigs, respectively. Serogroup II contains the type II heat-labile enterotoxin (LT-II) of E. coli. Two antigenic variants designated LT-IIa and LT-IIb have been described. The binding of CT, LTh-I, LT-IIa, and LT-IIb to gangliosides was analyzed by immunostaining thin-layer chromatograms and by solid-phase radioimmunoassay. The four toxins have different glycolipid-binding specificities. LTh-I and CT bind strongly to ganglioside GM1 and less strongly to ganglioside GD1b. However, LTh-I, unlike CT, also binds weakly to GM2 and asialo GM1. LTh-I, like CT, probably binds to the terminal sugar sequence Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal . . ., where GalNAc is N-acetylgalactosamine and NeuAc is N-acetylneuraminic acid. LT-IIa probably binds to the same sugar sequence to which CT and LTh-I bind, with the additional contribution to binding of a second NeuAc as in GD1b and GD2. Also, LT-IIa must bind the Gal beta 1-3GalNAc . . . sequence in such a way that its binding is relatively unaffected by attachment of NeuAc to the terminal galactose residue as in GD1a, GT1b, and GQ1b. LT-IIb probably binds to the terminal sugar sequence NeuAc alpha 2-3Gal beta 1-4GalNAc . . ., as it binds to gangliosides GD1a and GT1b but not to GM1.
Fukuta
S
S
Laboratory of Structural Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Magnani
J L
JL
Twiddy
E M
EM
Holmes
R K
RK
Ginsburg
V
V
D000311:Adrenal Glands / Q000166:cytology; D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D001921:Brain; D002236:Carbohydrate Conformation; D002417:Cattle; D002772:Cholera Toxin / Q000378:metabolism*; D004768:Enterotoxins / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D005333:Fetus; D005677:G(M1) Ganglioside; D006017:Glycolipids / Q000378:metabolism*; D006028:Glycosphingolipids / Q000378:metabolism; D051379:Mice; D009439:Neuraminidase; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000032:analysis* / Q000187:drug effects; D013329:Structure-Activity Relationship
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D006017:Glycolipids; D006028:Glycosphingolipids; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C033639:glycolipid receptor; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli; D009439:Neuraminidase