Myelin oligodendrocyte glycoprotein (MOG), is considered an important central-nervous system-specific target autoantigen for primary demyelination in autoimmune diseases like multiple sclerosis. We have recently demonstrated that MOG or its derived peptide, MOG-(35-55)-peptide, are able to produce in animals, clinicopathologic signs that mimic multiple sclerosis. The rat MOG sequence spanning amino acids 35-55 [rMOG-(35-55)-peptide] differs from the human sequence [hMOG-(35-55)-peptide] by a single amino acid substitution, i.e. Pro42-->Ser. Mice injected with rMOG-(35-55)-peptide showed severe inflammation and demyelination throughout the central nervous system but, interestingly, mice injected with hMOG-(35 -55)-peptide showed only a few foci of mild inflammation with no demyelination. Circular dichroism and nuclear magnetic resonance spectroscopy have been used to structurally characterise the bioactive peptides hMOG-(35-55)-peptide and rMOG-(35-55)-peptide. In 0.1 M K2HPO4/KOH, 90% H2O/D2O solutions, these derived peptides have been shown, by NMR spectroscopy, to adopt detectable levels of short-range structure in equilibrium with unfolded conformers. On addition of 2,2,2-trifluoro-(2H3)ethanol, rMOG-(35-55)-peptide and hMOG-(35-55)-peptide adopt folded structures which have nuclear Overhauser enhancements characteristic of a poorly defined alpha-helix over residues 44-51. There are some indications of secondary structure also evident in the N-terminal region of rMOG-(35-55)-peptide. CD spectroscopy has revealed that in aqueous solution both peptides are unfolded but in 2.2.2-trifluoroethanol and, at micellar concentrations of sodium dodecyl sulfate, rMOG-(35-55)-peptide and, to a lesser extent, hMOG-(35-55)-peptide adopt helical conformations. In contrast, at non-micellar concentrations of SDS rMOG-(35-55)-peptide and hMOG-(35-55)-peptide adopt, according to CD spectroscopy, a beta-structure indicating that the peptides change conformation depending on the microenvironment of the amino acids.
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| rdfs:comment |
Myelin oligodendrocyte glycoprotein (MOG), is considered an important central-nervous system-specific target autoantigen for primary demyelination in autoimmune diseases like multiple sclerosis. We have recently demonstrated that MOG or its derived peptide, MOG-(35-55)-peptide, are able to produce in animals, clinicopathologic signs that mimic multiple sclerosis. The rat MOG sequence spanning amino acids 35-55 [rMOG-(35-55)-peptide] differs from the human sequence [hMOG-(35-55)-peptide] by a single amino acid substitution, i.e. Pro42-->Ser. Mice injected with rMOG-(35-55)-peptide showed severe inflammation and demyelination throughout the central nervous system but, interestingly, mice injected with hMOG-(35 -55)-peptide showed only a few foci of mild inflammation with no demyelination. Circular dichroism and nuclear magnetic resonance spectroscopy have been used to structurally characterise the bioactive peptides hMOG-(35-55)-peptide and rMOG-(35-55)-peptide. In 0.1 M K2HPO4/KOH, 90% H2O/D2O solutions, these derived peptides have been shown, by NMR spectroscopy, to adopt detectable levels of short-range structure in equilibrium with unfolded conformers. On addition of 2,2,2-trifluoro-(2H3)ethanol, rMOG-(35-55)-peptide and hMOG-(35-55)-peptide adopt folded structures which have nuclear Overhauser enhancements characteristic of a poorly defined alpha-helix over residues 44-51. There are some indications of secondary structure also evident in the N-terminal region of rMOG-(35-55)-peptide. CD spectroscopy has revealed that in aqueous solution both peptides are unfolded but in 2.2.2-trifluoroethanol and, at micellar concentrations of sodium dodecyl sulfate, rMOG-(35-55)-peptide and, to a lesser extent, hMOG-(35-55)-peptide adopt helical conformations. In contrast, at non-micellar concentrations of SDS rMOG-(35-55)-peptide and hMOG-(35-55)-peptide adopt, according to CD spectroscopy, a beta-structure indicating that the peptides change conformation depending on the microenvironment of the amino acids.
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| skos:exactMatch | |
| uniprot:name |
Eur. J. Biochem.
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| uniprot:author |
Albouz-Abo S.,
Bernard C.C.A.,
Wilson J.C.,
von Itzstein M.
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| uniprot:date |
1997
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| uniprot:pages |
59-70
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| uniprot:title |
A conformational study of the human and rat encephalitogenic myelin oligodendrocyte glycoprotein peptides 35-55.
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| uniprot:volume |
246
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| dc-term:identifier |
doi:10.1111/j.1432-1033.1997.t01-2-00059.x
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