The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis.
Myelin oligodendrocyte glycoprotein (MOG) is a key CNS-specific autoantigen for primary demyelination in multiple sclerosis. Although the disease-inducing role of MOG has been established, its precise function in the CNS remains obscure. To gain new insights into the physiological and immunopathological role of MOG, we determined the 1.8-A crystal structure of the MOG extracellular domain (MOGED). MOGED adopts a classical Ig (Ig variable domain) fold that was observed to form an antiparallel head-to-tail dimer. A dimeric form of native MOG was observed, and MOGED was also shown to dimerize in solution, consistent with the view of MOG acting as a homophilic adhesion receptor. The MOG35-55 peptide, a major encephalitogenic determinant recognized by both T cells and demyelinating autoantibodies, is partly occluded within the dimer interface. The structure of this key autoantigen suggests a relationship between the dimeric form of MOG within the myelin sheath and a breakdown of immunological tolerance to MOG that is observed in multiple sclerosis.
Clements
Craig S
CS
Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3168, Australia.
Reid
Hugh H
HH
Beddoe
Travis
T
Tynan
Fleur E
FE
Perugini
Matthew A
MA
Johns
Terrance G
TG
Bernard
Claude C A
CC
Rossjohn
Jamie
J
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004591:Electrophoresis, Polyacrylamide Gel; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000378:metabolism*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry* / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D017386:Sequence Homology, Amino Acid
D001324:Autoantigens; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein