English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein

MPS-Authors
/persons/resource/persons39060

Schubart,  A.
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

Zander,  H.
Max Planck Society;

/persons/resource/persons38902

Huber,  R.
Max Planck Research Group: Behavioral Genetics / Tanimoto, MPI of Neurobiology, Max Planck Society;

/persons/resource/persons38969

Linington,  C.
Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Breithaupt, C., Schubart, A., Zander, H., Skerra, A., Huber, R., Linington, C., et al. (2003). Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein. Proceedings of the National Academy of Sciences of the United States of America, 100(16), 9446-9451.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0012-230C-A
Abstract
Multiple sclerosis is a chronic disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal loss. The immunopathogenesis of demyelination in multiple sclerosis involves an autoantibody response to myelin oligodendrocyte glycoprotein (MOG), a type I transmembrane protein located at the surface of CNS myelin. Here we present the crystal structures of the extracellular domain of MOG (MOG(Igd)) at 1.45-Angstrom resolution and the complex of MOG(Igd) with the antigen-binding fragment (Fab) of the MOG-specific demyelinating monoclonal antibody 8-18C5 at 3.0-Angstrom resolution. MOG(Igd) adopts an IgV like fold with the A'GFCC'C" sheet harboring a cavity similar to the one used by the costimulatory molecule B7-2 to bind its ligand CTLA4. The antibody 8-18C5 binds to three loops located at the membrane-distal side of MOG with a surprisingly dominant contribution made by MOG residues 101-108 containing a strained loop that forms the upper edge of the putative ligand binding site. The sequence R(101)DHSYQEE(108) is unique for MOG, whereas large parts of the remaining sequence are conserved in potentially tolerogenic MOG homologues expressed outside the immuno-privileged environment of the CNS. Strikingly, the only sequence identical to DHSYQEE was found in a Chlamydia trachomatis protein of unknown function, raising the possibility that Chlamydia infections may play a role in the MOG-specific autoimmune response in man. Our data provide the structural basis for the development of diagnostic and therapeutic strategies targeting the pathogenic autoantibody response to MOG.