All About Multiple Sclerosis

More MS news articles for August 2003

How antibodies bind to MOG and what this might mean

July 31, 2003
Boston Cure Project

A very interesting new study from a team of researchers in Germany sheds new light on one feature of MS pathology. This team sought to study the molecular interactions between myelin oligodendrocyte glycoprotein (MOG) and the anti-MOG antibodies which have been found in MS plaques and which may play a role in the demyelination that occurs in MS. Understanding this interaction might eventually lead a means of blocking it and thereby possibly stopping or slowing demyelination.

One of the things that the researchers wanted to find out was exactly what part of the MOG molecule was being targeted by the antibodies. Scientists had already tried searching for individual segments of MOG that would bind to these autoantibodies, but without success. Whether an antibody will bind to a molecule is based on their shapes (kind of like whether a key will fit into a lock), so it is likely that the little pieces of MOG that were studied were too small to fold up into their natural shape and therefore failed to bind to the antibodies. So this team took a different approach, which was to crystallize a larger MOG sequence (the entire part that sticks out of the cell and is thus exposed to antibodies), as well as a particular MOG/antibody combination, and use techniques for finding the 3D crystalline structure of molecules to get an understanding of the shapes involved.

Mapping the crystalline structure of the extracellular part of MOG revealed similarities to other molecules, which might provide clues as to what MOG does (right now nobody knows what MOG's function is). Mapping the MOG/antibody combination showed exactly where this particular antibody binds (the outermost end of the MOG molecule). There are a number of interesting things about this particular part of the molecule. First, it has a sharp bend which small individual MOG fragments wouldn't be able to form (which explains the failure of those previous tests). Second, it contains a fold which might under normal conditions bind a useful molecule, so perhaps antibody binding to this spot is harmful because it inhibits normal oligodendrocyte functioning in some way. Third, this MOG site contains a sequence which is somewhat unique to MOG in the human body, so it doesn't have any close relatives floating around in the body inducing immune tolerance to it -- and therefore it might be particularly vulnerable to an immune response. And fourth, this same sequence is very similar to sequences found in Chlamydia, a bacterial species that has been associated with MS, so perhaps MS can be triggered by a Chlamydia infection which sets off an immune response that also happens to be destructive of MOG.

Clearly this paper raises a number of interesting ideas -- how they will play out remains to be seen. However, we're now closer to understanding one of the molecular interactions that might drive MS, which has direct applicability to the development of treatments for the disease.

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