A unique multifucosylated -3GalNAc beta 1-->4GlcNAc beta 1-->3Gal alpha 1- motif constitutes the repeating unit of the complex O-glycans derived from the cercarial glycocalyx of Schistosoma mansoni.
The entire surface of the cercarial stage of the human blood fluke Schistosoma mansoni is covered by a 1-microns thick, highly immunogenic, fucose-rich glycocalyx (GCX). Using strategies based on enzymatic, chemical, and mass spectrometric analysis, we have defined the structures of the major glycans released by reductive elimination from GCX. They comprise a heterogeneous population of multifocosylated complex oligosaccharides with the following nonreducing terminal sequences: [formula: see text] Our structural data suggest that these tri- to pentafucosylated epitopes are carried on type 1, R-->Gal beta-1-->3GalNAc, and type 2, R-->Gal beta 1-->3(R-->GlcNAc beta-1-->6)GalNAc, core structures via repeat units of (3GalNAc beta 1-->4(Fuc alpha 1-->2Fuc alpha 1-->2Fuc alpha 1-->3)GlcNAc beta-1-->3Gal alpha-->)n, where n is mainly 0 and 1, and all sugars are in the pyranose form. The proposed structure represents the first instance where an alpha-galactosylated beta-GalNAc(1-->4)-beta-GlcNAc sequence occurs as a repeating unit in a glycoprotein. It is also unique in being substituted with oligofucosyl appendages. The unusual oligosaccharide structures described here, particularly the potentially immunodominant oligofucosyl moieties, are most likely responsible for the known potency of GCX in modulating various immune responses including complement activation, B cell mitogenesis, and delayed type hypersensitivity in schistosomiasis.
Khoo
K H
KH
Department of Biochemistry, Imperial College, London, United Kingdom.
Sarda
S
S
Xu
X
X
Caulfield
J P
JP
McNeil
M R
MR
Homans
S W
SW
Morris
H R
HR
Dell
A
A
D000818:Animals; D002240:Carbohydrate Sequence; D006023:Glycoproteins / Q000737:chemistry* / Q000502:physiology; D006026:Glycoside Hydrolases / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry* / Q000502:physiology; D012550:Schistosoma mansoni / Q000737:chemistry*; D005644:alpha-L-Fucosidase / Q000494:pharmacology
D006023:Glycoproteins; D011134:Polysaccharides; D006026:Glycoside Hydrolases; D005644:alpha-L-Fucosidase