title: Three-dimensional structure of myelin basic protein. II. Molecular modeling and considerations of predicted structures in multiple sclerosis.
abstract: A computational model of myelin basic protein (MBP) has been constructed based on the premise of a phylogenetically conserved beta-sheet backbone and on electron microscopical three-dimensional reconstructions. Many residues subject to post-translational modification (phosphorylation, methylation, or conversion of arginines to citrullines) were located in loop regions and thus accessible to modifying enzymes. The triproline segment (residues 99-101) is fully exposed on the back surface of the protein in a long crossover connection between two parallel beta-strands. The proximity of this region to the underlying beta-sheet suggests that post-translational modifications here might have potential synergistic effects on the entire structure. Post-translational modifications that lead to a reduced surface charge could result first in a weakened attachment to the myelin membrane rather than in a gross conformational change of the protein itself. Such mechanisms could be operative in demyelinating diseases such as multiple sclerosis.
authors.affiliation: Department of Molecular Biology and Genetics, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
authors.forename: R A
authors.initials: RA
authors.lastname: Ridsdale
authors.forename: D R
authors.initials: DR
authors.lastname: Beniac
authors.forename: T A
authors.initials: TA
authors.lastname: Tompkins
authors.forename: M A
authors.initials: MA
authors.lastname: Moscarello
authors.forename: G
authors.initials: G
authors.lastname: Harauz
mesh_terms: D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D009103:Multiple Sclerosis / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D004676:Myelin Basic Protein