Effect of structural modifications of ganglioside GM2 on intra-molecular carbohydrate-to-carbohydrate interaction and enzymatic susceptibility.
The effect of inter-molecular carbohydrate-to-carbohydrate interaction on basic cell biological processes has been well documented and appreciated. In contrast, very little is known about the intra-molecular carbohydrate-to-carbohydrate interaction. The presence of an interaction between the GalNAc and the Neu5Ac in GM2 detected by NMR spectroscopy represents a well-defined intra-molecular carbohydrate-to-carbohydrate interaction. This intriguing interaction is responsible for the GM2-epitope, GalNAcbeta1-->4(Neu5Acalpha2-->3)Gal-, to exhibit a rigid and compact conformation. We hypothesized that this compact conformation may be the cause for both the GalNAc and the Neu5Ac in GM2 to be refractory to enzymatic hydrolysis and the GM2 activator protein is able to interact with the compact trisaccharide GM2-epitope, rendering the GalNAc and the Neu5Ac accessible to beta-hexosaminidase A and sialidase. We have used a series of structurally modified GM2 to study the effect of modifications of sugar chains on the conformation and enzymatic susceptibility of this ganglioside. Our hypothesis was borne out by the fact that when the GalNAcbeta1-->4Gal linkage in GM2 was converted to the GalNAcbeta1-->6Gal, both the GalNAc and the Neu5Ac became susceptible to beta-hexosaminidase A and sialidase, respectively, without GM2 activator protein. We hope our work will engender interest in identifying other intra-molecular carbohydrate-to-carbohydrate interactions in glycoconjugates.
Li
Yu-Teh
YT
Department of Biochemistry, Tulane University Health Sciences Center School of Medicine, New Orleans, LA 70112 USA. yli1@tulane.edu
Li
Su-Chen
SC
Kiso
Makoto
M
Ishida
Hideharu
H
Mauri
Laura
L
Raimondi
Laura
L
Bernardi
Anna
A
Sonnino
Sandro
S
D000116:Acetylgalactosamine / Q000737:chemistry / Q000378:metabolism; D002236:Carbohydrate Conformation; D002855:Chromatography, Thin Layer; D000939:Epitopes / Q000737:chemistry; D005678:G(M2) Ganglioside / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism*; D005690:Galactose / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D009154:Mutation / Q000235:genetics; D009439:Neuraminidase / Q000378:metabolism*; D011522:Protons; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism*
D000939:Epitopes; D011522:Protons; D005678:G(M2) Ganglioside; D009439:Neuraminidase; D001619:beta-N-Acetylhexosaminidases; D000116:Acetylgalactosamine; D005690:Galactose