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Taxonomic group: bacteria / Proteobacteria (Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: infection due to Campylobacter jejuni [ICD11: XN4Q5

]

The structure was elucidated in this paper
NCBI PubMed ID: 17198373
Publication DOI: 10.1021/bi062001v
Journal NLM ID: 0370623
Publisher: American Chemical Society
Correspondence: Michel.Gilbert

nrc-cnrc.gc.ca
Institutions: Institute for Biological Sciences, National Research Council Canada, Ottawa, Ontario K1A 0R6, Canada

The enteropathogen Campylobacter jejuni has the ability to synthesize glycan structures that are similar to mammalian gangliosides within the core component of its lipooligosaccharide (LOS). Exposure to ganglioside mimics in some individuals results in the production of autoantibodies that deleteriously attack nerve surface gangliosides, precipitating the onset of Guillain-Barre and Fisher syndromes (GBS and FS). We have characterized the interaction of four monoclonal antibodies (mAbs), established by sensitization of mice with LOS isolated from GBS- and FS-associated C. jejuni strains, with chemoenzymatically synthesized gangliooligosaccharides. Surface plasmon resonance (SPR) measurements demonstrate that three of the mAbs interact specifically with derivatives corresponding to their targeted gangliosides, with dissociation constants ranging from 10 to 20 microM. Antibody binding to the gangliooligosaccharides was probed by saturation transfer difference (STD) NMR spectroscopy. STD signals, resulting from antibody/oligosaccharide interaction, were observed for each of the four mAbs. In two cases, differential saturation transfer rates to oligosaccharide resonances enabled detailed epitope mapping. The binding of GD1a-S-Phe with GB1 is characterized by close association of the immunoglobulin with sites that are distributed over several residues of the oligosaccharide. This contrasts sharply with the profile observed for the binding of both GD3-S-Phe and GT1a-S-Phe with FS1. The close antigenic contacts in these ganglioside derivatives are confined to the N-acetylmannosaminyl portion of the terminal N-acetylneuraminic acid (NeuAc) residue of the disialosyl moiety. Our characterization of FS1 provides insight, at an atomic level, into how a single antigenic determinant presented by the LOS of C. jejuni can give rise to antibodies with binding promiscuity to [αNeuAc-(2-8)-αNeuAc]-bound epitopes and demonstrates why sera from FS patients have antibodies that are often reactive with more than one disialylated ganglioside

LOS, monoclonal antibodies, Campylobacter jejuni, gangliosides, Guillain-Barre syndrome, Miller Fisher syndrome, Surface Plasmon Resonance, Epitope Mapping, Binding Sites

Structure type: oligomer
Location inside paper: p.38, fig.1 GT1a-S-Phe
Aglycon: phenylthio
Trivial name: gangliooligosaccharide
Contained glycoepitopes: IEDB_130648,IEDB_134627,IEDB_136044,IEDB_136794,IEDB_137472,IEDB_137473,IEDB_141794,IEDB_146100,IEDB_147450,IEDB_147451,IEDB_149174,IEDB_150933,IEDB_150937,IEDB_153198,IEDB_153199,IEDB_1625329,IEDB_190606,SB_116,SB_165,SB_166,SB_170,SB_171,SB_172,SB_187,SB_195,SB_23,SB_24,SB_25,SB_35,SB_39,SB_42,SB_68,SB_7,SB_70,SB_8,SB_84,SB_88,SB_96,SB_97

Methods: 13C NMR, 1H NMR, NMR-2D, serological methods, biochemical methods, STD NMR, surface plasmon resonance (SPR)
Biological activity: serological data
Synthetic data: chemoenzymatic
Comments, role: gangliooligosaccharide like GT1a
3D data: molecular modeling

Related record ID(s): 21556, 21929, 21930
NCBI Taxonomy refs (TaxIDs): 197
Reference(s) to other database(s): GlycomeDB:608
Show glycosyltransferases

NMR conditions: in D2O at 298 K [as TSV]

13C NMR data:
Linkage	Residue	C1	C2	C3	C4	C5	C6	C7	C8	C9
4,3,5	Ac	?	22.9
4,3	aXNeup	?	?	38.3	69.5	52.4	73.8	69.0	73.1	63.7
4,4,3,3,8,5	Ac	?	22.9
4,4,3,3,8	aXNeup	?	?	41.4	69.4	52.6	73.4	69.0	72.7	63.5
4,4,3,3,5	Ac	?	23.2
4,4,3,3	aXNeup	?	?	40.5	69.0	53.1	75.0	70.3	79.3	62.5
4,4,3	bDGalp	105.3	70.0	76.1	68.3	75.3	61.9
4,4,2	Ac	?	23.5
4,4	bDGalpN	103.4	51.9	81.0	68.6	75.1	62.0
4	bDGalp	103.3	70.8	75.2	77.3	74.9	61.5
	bDGlcp1S	87.9	72.2	76.6	79.5	79.0	61.0


1H NMR data:
Linkage	Residue	H1	H2	H3	H4	H5	H6	H7	H8	H9
4,3,5	Ac	-	2.04
4,3	aXNeup	-	-	1.90-2.70	3.76	3.82	3.51	3.58	3.76	3.62-3.87
4,4,3,3,8,5	Ac	-	2.04
4,4,3,3,8	aXNeup	-	-	1.74-2.77	3.67	3.83	3.61	3.59	3.92	3.65-3.89
4,4,3,3,5	Ac	-	2.07
4,4,3,3	aXNeup	-	-	1.75-2.66	3.60	3.80	3.63	3.85	4.16	3.71-4.17
4,4,3	bDGalp	4.61	3.54	4.08	3.97	3.68	3.72
4,4,2	Ac	-	2.03
4,4	bDGalpN	4.75	4.02	3.85	4.16	3.70	3.76
4	bDGalp	4.52	3.38	4.13	4.10	3.74	3.76-3.80
	bDGlcp1S	4.84	3.40	3.69	3.63	3.63	3.80-3.97


1H/13C HSQC data:
Linkage	Residue	C1/H1	C2/H2	C3/H3	C4/H4	C5/H5	C6/H6	C7/H7	C8/H8	C9/H9
4,3,5	Ac		22.9/2.04
4,3	aXNeup			38.3/1.90-2.70	69.5/3.76	52.4/3.82	73.8/3.51	69.0/3.58	73.1/3.76	63.7/3.62-3.87
4,4,3,3,8,5	Ac		22.9/2.04
4,4,3,3,8	aXNeup			41.4/1.74-2.77	69.4/3.67	52.6/3.83	73.4/3.61	69.0/3.59	72.7/3.92	63.5/3.65-3.89
4,4,3,3,5	Ac		23.2/2.07
4,4,3,3	aXNeup			40.5/1.75-2.66	69.0/3.60	53.1/3.80	75.0/3.63	70.3/3.85	79.3/4.16	62.5/3.71-4.17
4,4,3	bDGalp	105.3/4.61	70.0/3.54	76.1/4.08	68.3/3.97	75.3/3.68	61.9/3.72
4,4,2	Ac		23.5/2.03
4,4	bDGalpN	103.4/4.75	51.9/4.02	81.0/3.85	68.6/4.16	75.1/3.70	62.0/3.76
4	bDGalp	103.3/4.52	70.8/3.38	75.2/4.13	77.3/4.10	74.9/3.74	61.5/3.76-3.80
	bDGlcp1S	87.9/4.84	72.2/3.40	76.6/3.69	79.5/3.63	79.0/3.63	61.0/3.80-3.97

¹H NMR data:

Linkage	Residue	H1	H2	H3	H4	H5	H6	H7	H8	H9
4,3,5	Ac		2.04
4,3	aXNeup			1.90 2.70	3.76	3.82	3.51	3.58	3.76	3.62 3.87
4,4,3,3,8,5	Ac		2.04
4,4,3,3,8	aXNeup			1.74 2.77	3.67	3.83	3.61	3.59	3.92	3.65 3.89
4,4,3,3,5	Ac		2.07
4,4,3,3	aXNeup			1.75 2.66	3.60	3.80	3.63	3.85	4.16	3.71 4.17
4,4,3	bDGalp	4.61	3.54	4.08	3.97	3.68	3.72
4,4,2	Ac		2.03
4,4	bDGalpN	4.75	4.02	3.85	4.16	3.70	3.76
4	bDGalp	4.52	3.38	4.13	4.10	3.74	3.76 3.80
	bDGlcp1S	4.84	3.40	3.69	3.63	3.63	3.80 3.97

¹³C NMR data:

Linkage	Residue	C1	C2	C3	C4	C5	C6	C7	C8	C9
4,3,5	Ac	?	22.9
4,3	aXNeup	?	?	38.3	69.5	52.4	73.8	69.0	73.1	63.7
4,4,3,3,8,5	Ac	?	22.9
4,4,3,3,8	aXNeup	?	?	41.4	69.4	52.6	73.4	69.0	72.7	63.5
4,4,3,3,5	Ac	?	23.2
4,4,3,3	aXNeup	?	?	40.5	69.0	53.1	75.0	70.3	79.3	62.5
4,4,3	bDGalp	105.3	70.0	76.1	68.3	75.3	61.9
4,4,2	Ac	?	23.5
4,4	bDGalpN	103.4	51.9	81.0	68.6	75.1	62.0
4	bDGalp	103.3	70.8	75.2	77.3	74.9	61.5
	bDGlcp1S	87.9	72.2	76.6	79.5	79.0	61.0

The spectrum also has 10 signals at unknown positions (not plotted).

There is only one chemically distinct structure:

CC(=O)N[C@@H]1[C@@H](O)C[C@](O[C@H]2[C@@H](O)[C@@H](CO)O[C@@H](O[C@@H]3[C@@H](NC(C)=O)[C@H](O[C@H]4[C@@H](CO)O[C@@H](O[C@@H]5[C@@H](CO)O[C@@H](S)[C@H](O)[C@H]5O)[C@H](O)[C@H]4O[C@]4(C(=O)O)C[C@H](O)[C@@H](NC(C)=O)[C@H]([C@H](O)[C@H](O)CO)O4)O[C@H](CO)[C@@H]3O)[C@@H]2O)(C(=O)O)O[C@H]1[C@H](O)[C@@H](CO)O[C@]1(C(=O)O)C[C@H](O)[C@@H](NC(C)=O)[C@H]([C@H](O)[C@H](O)CO)O1

SVG MW SMILES 3D mol Ionize