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 de myelination in autoimmune diseases such as multiple sclerosis (MS). The nat ive structure of MOG presents a glycosylation site at position 31 (Asn(31)) . It has been recently described that glycosylation of a MOG peptide epitop e improved the detection of specific autoantibodies in sera of MS patients. The solution conformational behavior of two MOG derived peptides-hMOG(30-5 0) (1) and the glycosylated analogue [Asn(31)(N-beta -Glc)]hMOG(30-50) (2)- were investigated through NMR analysis in a water/HFA solution. Conformatio nal 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-termi nal 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 differen ce between peptides 1 and 2. Thus, the specific antibody recognition of pep tide 2 is most likely driven by direct interactions of the antibody binding site with the Asn-linked sugar moiety.