Helical epitope of the group B meningococcal alpha(2-8)-linked sialic acid polysaccharide.
The immunological properties of the group B meningococcal alpha(2-8)-linked sialic acid polysaccharide have been rationalized in terms of a model where the random coil nature of the polymer can be described by the presence of local helices. The conformational versatility of the alpha NeuAc(2-8)alpha NeuAc linkage has been explored by NMR studies at 600 MHz in conjunction with potential energy calculations for colominic acid, an alpha(2-8)NeuAc polymer, and the trisaccharide alpha NeuAc(2-8)alpha NeuAc(2-8)beta NeuAc. Potential energy calculations were used to estimate the energetically favorable conformers and to describe the wide range of helices which the polymer can adopt. No unique conformer was found to satisfy all NMR constraints, and only ensemble averaged nuclear Overhauser enhancements could correctly simulate the experimental data. Conformational differences between the polymer and the trisaccharide could be best explained in terms of slight changes in the relative distribution of conformers in solution. Similar helical parameters for the alpha(2-8)NeuAc polymer and poly(A) were proposed as the basis for their cross-reactivity to a monoclonal antibody IgMNOV. The unusual length dependency for binding of oligosaccharide to group B specific antibodies was postulated to arise from the recognition of a high-order local helix with an extended conformation which was not highly populated in solution.
Brisson
J R
JR
Institute for Biological Sciences, National Research Council of Canada, Ottawa.
Baumann
H
H
Imberty
A
A
Pérez
S
S
Jennings
H J
HJ
D000942:Antigens, Bacterial / Q000737:chemistry*; D016667:Bacterial Capsules; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D000939:Epitopes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000276:immunology; D012794:Sialic Acids / Q000737:chemistry
D000942:Antigens, Bacterial; D000939:Epitopes; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial; D012794:Sialic Acids; C071290:alpha(2-8)polysialic acid; C039455:capsular polysaccharide, meningococcal group B; C014420:colominic acid