NMR studies of carbohydrates and carbohydrate-mimetic peptides recognized by an anti-group B Streptococcus antibody.
As part of a program to investigate the origins of peptide-carbohydrate mimicry, the conformational preferences of peptides that mimic the group B streptococcal type III capsular polysaccharide have been investigated by NMR spectroscopy. Detailed studies of a dodecapeptide, FDTGAFDPDWPA, a molecular mimic of the polysaccharide antigen, and two new analogs, indicated a propensity for beta-turn formation. Different beta-turn types were found to be present in the trans and cis (Trp-10-Pro-11) isomers of the peptide: the trans isomer favored a type I beta-turn from residues Asp-7-Trp-10, whereas the cis isomer exhibited a type VI beta-turn from residues Asp-9-Ala-12. The interaction of the dodecapeptide FDTGAFDPDWPA with a protective anti-group B Streptococcus monoclonal antibody has also been investigated, by transferred nuclear Overhauser effect NMR spectroscopy and saturation-transfer difference NMR spectroscopy (STD-NMR). The peptide was found to adopt a type I beta-turn conformation on binding to the antibody; the peptide residues (Asp-7-Trp-10) forming this turn are recognized by the antibody, as demonstrated by STD-NMR experiments. STD-NMR studies of the interactions of oligosaccharide fragments of the capsular polysaccharide have also been performed and provide evidence for the existence of a conformational epitope.
Johnson
Margaret A
MA
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
Jaseja
Mahesh
M
Zou
Wei
W
Jennings
Harold J
HJ
Copie
Valérie
V
Pinto
B Mario
BM
Pincus
Seth H
SH
D000907:Antibodies, Bacterial / Q000276:immunology; D000918:Antibody Specificity; D018604:Epitope Mapping; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation; D013292:Streptococcus agalactiae / Q000737:chemistry / Q000276:immunology*
D000907:Antibodies, Bacterial; D010455:Peptides; D011135:Polysaccharides, Bacterial