Three-dimensional structure of myelin basic protein. II. Molecular modeling and considerations of predicted structures in multiple sclerosis.
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.
Ridsdale
R A
RA
Department of Molecular Biology and Genetics, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
Beniac
D R
DR
Tompkins
T A
TA
Moscarello
M A
MA
Harauz
G
G
D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D009103:Multiple Sclerosis / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
D004676:Myelin Basic Protein