Background and Significance

Myelin is a specialized membrane structure in the vertebrate nervous system, enabling the fast ‘saltatory’ conduction of nerve impulses. The myelin sheath is formed by the differentiated plasma membrane of a myelinating glial cell (Schwann cell or oligodendrocyte), which wraps itself tightly around the axon, forming a compact multilayered membrane complex with a very low solvent content. Biochemically, myelin is a unique membrane, and most major myelin proteins are specific to myelin. Essentially all of the myelin-specific proteins interact intimately with lipid bilayers, being either integral or peripheral membrane proteins. Despite a large volume of literature on myelin proteins, their structure and function are poorly characterized at the molecular level. To date, little is still known about the 3D structures of myelin-specific proteins and their complexes with other molecules, and myelin proteins represent a gap in our knowledge of the 3D structure of the protein universe. In addition to being specific to myelin, myelin proteins, in general, share little homology with proteins from other tissues or lower organisms.

Detailed structure-function information will be crucial to understanding the physiological function of myelin proteins. Neurological diseases, including multiple sclerosis and peripheral neuropathies, occur upon autoimmune attack against myelin or because of inherited mutations in myelin protein genes. Understanding of such diseases will be enhanced by accurate 3D structural data on myelin molecules and their interactions with each other and with ligands, including lipid membranes.

We aim to answer long-standing questions in myelin biology, specifically related to the relationships between structure, dynamics and function in individual myelin proteins and the factors contributing to these properties. Specific points of interest include how these molecules interact with membranes and the cytoskeleton, how they are arranged on the membrane, and how they contribute to the formation and maintenance of the compact structure of myelin.

Viimeksi päivitetty: 28.10.2016