Conformational analysis of a glycosylated human myelin oligodendrocyte glycoprotein peptide epitope able to detect antibody response in multiple sclerosis.
Myelin oligodendrocyte glycoprotein (MOG), a minor myelin component, is an important central nervous system specific target autoantigen for primary demyelination in autoimmune diseases such as multiple sclerosis (MS). The native structure of MOG presents a glycosylation site at position 31 (Asn(31)). It has been recently described that glycosylation of a MOG peptide epitope improved the detection of specific autoantibodies in sera of MS patients. The solution conformational behavior of two MOG derived peptides-hMOG(30-50) (1) and the glycosylated analogue [Asn(31)(N-beta-Glc)]hMOG(30-50) (2)-were investigated through NMR analysis in a water/HFA solution. Conformational studies revealed that peptides 1 and 2 adopted similar conformations in this environment. In particular, they showed strong propensity to assume a well-defined amphipatic structure encompassing residues 41-48. The N-terminal region resulted to be almost completely unstructured for both peptides. The presence in 1 of a low populated Asx-turn conformation characteristic of the Asn-Xaa-Thr glycosylation sites was the only conformational difference between peptides 1 and 2. Thus, the specific antibody recognition of peptide 2 is most likely driven by direct interactions of the antibody binding site with the Asn-linked sugar moiety.
Carotenuto
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A
Department of Pharmaceutical Sciences, University of Salerno, I-84084 Fisciano, Italy.
D'Ursi
A M
AM
Nardi
E
E
Papini
A M
AM
Rovero
P
P
D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000737:chemistry*; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000737:chemistry*; D000939:Epitopes; D006031:Glycosylation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000737:chemistry*; D011487:Protein Conformation
D000954:Antigens, Surface; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein