Structural biology of the formation and disease of the multilayered myelin membrane
Multiple sources (Focus area spearhead projects)
University of Oulu
Our project focuses on the structural biology of the myelin sheath, a unique biological structure crucial for the functioning of the nervous system in humans and other vertebrates. Myelin proteins play intimate roles in the formation of the multilayered myelin membrane, and mutations in - or autoimmune reactions towards – them are central in myelin diseases, such as multiple sclerosis (MS) and inherited neuropathies.
Our main overall goals are as follows:
- Structural and functional basis of point mutations linked to the human peripheral neuropathy CMT (Charcot-Marie-Tooth disease).
- Structure determination for several integral membrane proteins specifically expressed in the vertebrate myelin sheath.
- Structure and dynamics of myelin-like membranes with close biochemical resemblance to native myelin. We will expand our earlier work towards more complex molecular systems and higher-resolution experimental techniques.
A number of our goals have the potential to provide scientific breakthroughs in the field of myelin research. The project will help understand molecular neurodevelopment and the molecular etiology of human neurological diseases.
Raasakka A., Linxweiler H., Brophy P.J., Sherman D.L. & Kursula P. (2019) Direct binding of the flexible C-terminal segment of periaxin to β4 integrin suggests a molecular basis for CMT4F. Front. Mol. Neurosci. 12:84.
Raasakka A., Ruskamo S., Barker R., Krokengen O.C., Vatne G.H., Kristiansen C.K., Hallin E.I., Skoda M.W.A., Wacklin-Knecht H., Jones N.C., Hoffmann S.V. & Kursula P. (2019) Neuropathy-related mutations alter the membrane binding properties of the human myelin protein P0 cytoplasmic tail. PLoS ONE, 14:e0216833.
Raasakka A., Ruskamo S., Kowal J., Han H., Baumann A., Myllykoski M., Fasano A., Rossano R., Riccio P., Bürck J., Ulrich A.S., Stahlberg H. & Kursula P. (2019) Molecular structure and function of myelin protein P0 in membrane stacking. Sci. Rep. 9:642.
Myllykoski M., Eichel M.A., Jung R.B., Kelm S., Werner H.B & Kursula P. (2018) High-affinity heterotetramer formation between the large myelin-associated glycoprotein and the dynein light chain DYNLL1. J. Neurochem. 147:764-783.
Hallin E.I., Eriksen M.S., Baryshnikov S., Nikolaienko O., Grødem S., Hosokawa T., Hayashi Y., Bramham C.R. & Kursula P. (2018) Structure of monomeric full-length ARC sheds light on molecular flexibility, protein interactions, and functional modalities. J. Neurochem. 120:323-343.
Ruskamo S., Nieminen T., Kristiansen C.K., Vatne G.H., Baumann A., Hallin E.I., Raasakka A., Joensuu P., Bergmann U., Vattulainen I. & Kursula P. (2017) Molecular mechanisms of Charcot-Marie-Tooth neuropathy linked to mutations in human myelin protein P2. Sci. Rep. 7:6510.