Molecule of the Month: Myelin-associated Glycoprotein

Nerve cells face a challenging problem: cells are small, but the human body is large. The nervous system needs to communicate over long distances, but using small parts. Nerve cells solve this problem by sending signals down long, thin axons, some over a meter in length but only a few microns across. These delicate axons are often surrounded by a sheath of myelin, which protects and strengthens them and also creates a narrow, insulated space that rapidly propagates signals along the axon.

A collection of specialized proteins control the construction and maintenance of the myelin sheath. The one shown here, myelin-associated glycoprotein (MAG), forms a bridge between the myelin and the axon (PDB entry 5lf5). It forms a dimeric assembly embedded in the myelin membrane. The structure includes the portion of the protein that is outside the cell, showing how it reaches across the space between the cells and binds to specialized lipids on the surface of the axon membrane. MAG also has non-structured tails that extend into the myelinating cell and interact with regulatory and structural proteins inside.

Myelin is formed by specialized cells that wrap themselves around and around the axon. In the central nervous system, oligodendrocytes reach out with tendrils to several neighboring axons and form these amazing structures. Specialized proteins such as MAG, myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and others control the process and glue everything together.

A combination of genetic and environmental problems can cause the immune system to attack one or more myelin proteins, leading to the destruction of the myelin sheath and causing the disease multiple sclerosis. The two structures shown here capture events in this terrible process. PDB entry 1pkq shows an antibody bound to MOG, which disrupts its function on the outer surface of the sheath. PDB entry 1bx2 shows a peptide from MBP being displayed by MHC, which will lead to mobilization of the immune system against MBP. PDB entry 1h15 (not shown) is complex of MHC with a similar viral peptide, showing how a viral infection can lead to immune responses that then cross react with normal proteins such as MBP.