Conformation of the Oligosaccharide Chain of G M1 Ganglioside in a Carbohydrate-Enriched Surface

Abstract

The solution structure of ganglioside G M1 carbohydrate moiety at the surface of a 102-kDa lipid-modified-G M1 micelle is investigated by high-resolution 1H-NMR in H 2O. The micellar surface can be considered a cluster-like lateral distribution of the gangliosides, each single monomer being anchored in a carbohydrate-enriched model membrane matrix. 1H NOESY measurements at short mixing times reveal a rigid trisaccharide core - β-GalNAc-(1–4)-[ α-Neu5Ac-(2–3)]- β-Gal- and a more flexible β-Gal-(1–3)- β-GalNAc- terminal glycosidic bond. In the lipid-modified G M1 ganglioside micellar system, there is no evidence that intermolecular side-by-side carbohydrate interactions modulate, or alter in any way, the head-group spatial arrangement. Possible intermonomer interactions at the level of the branched trisaccharide portion were further investigated on mixed micelles of natural N-glycolyl- and N-acetylneuraminic acid containing G M1 in D 2O, taking advantage of the different NMR features of N-glycolyl- and N-acetylneuraminic acids, which allow discrimination between sialic acid ring proton signals. Measurements of the water/ganglioside-OH proton chemical exchange rates suggest hydroxyl group involvement at position 8 of sialic acid in strong intramolecular interaction processes.