Open AccessA Conformational Study of the Human and Rat Encephalitogenic Myelin Oligodendrocyte Glycoprotein Peptides 35–55
Author(s) -
AlbouzAbo Samia,
Wilson Jennifer C.,
Bernard Claude C. A.,
Itzstein Mark
Publication year - 1997
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1997.t01-2-00059.x
Subject(s) - peptide , myelin oligodendrocyte glycoprotein , chemistry , circular dichroism , peptide sequence , epitope , nuclear magnetic resonance spectroscopy , peptide conformation , biochemistry , myelin , amino acid , protein secondary structure , multiple sclerosis , experimental autoimmune encephalomyelitis , central nervous system , stereochemistry , biology , antibody , immunology , endocrinology , gene
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 snowed 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 K 2 HPO 4 /KOH, 90% H 2 O/D 2 O 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‐( 2 H 3 )ethanol, rMOG‐(35–55)‐peptide and hMOG‐(35–55)‐peptide adopt folded structures which have nuclear Overhauser enhancements characteristic of a poorly defined α‐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 β‐structure indicating that the peptides change conformation depending on the micro‐environment of the amino acids.