Raasakka, A., Ruskamo, S., Kowal, J., Barker, R., Baumann, A., Martel, A., Tuusa, J., Myllykoski, M., Bürck, J., Ulrich, A., Stahlberg, H., Kursula, P. (2017) Membrane Association Landscape of Myelin Basic Protein Portrays Formation of the Myelin Major Dense Line. Scientific Reports, 7 (1), . doi:10.1038/s41598-017-05364-3
Membrane association landscape of myelin basic protein portrays formation of the myelin major dense line
|Author:||Raasakka, Arne1,2; Ruskamo, Salla2; Kowal, Julia3;|
1Department of Biomedicine, University of Bergen
2Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu
3Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum, University of Basel
4School of Physical Sciences, University of Kent
5Institut Laue-Langevin (ILL)
6Division of Psychiatry, Haukeland University Hospital
7Institute of Biological Interfaces (IBG-2), Karlsruhe Institute of Technology
8Institute of Organic Chemistry, Karlsruhe Institute of Technology
|Online Access:||PDF Full Text (PDF, 5.8 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe201708248202
Nature Publishing Group,
|Publish Date:|| 2017-08-24
AbstractCompact myelin comprises most of the dry weight of myelin, and its insulative nature is the basis for saltatory conduction of nerve impulses. The major dense line (MDL) is a 3-nm compartment between two cytoplasmic leaflets of stacked myelin membranes, mostly occupied by a myelin basic protein (MBP) phase. MBP is an abundant myelin protein involved in demyelinating diseases, such as multiple sclerosis. The association of MBP with lipid membranes has been studied for decades, but the MBP-driven formation of the MDL remains elusive at the biomolecular level. We employed complementary biophysical methods, including atomic force microscopy, cryo-electron microscopy, and neutron scattering, to investigate the formation of membrane stacks all the way from MBP binding onto a single membrane leaflet to the organisation of a stable MDL. Our results support the formation of an amorphous protein phase of MBP between two membrane bilayers and provide a molecular model for MDL formation during myelination, which is of importance when understanding myelin assembly and demyelinating conditions.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This work was financially supported by the Academy of Finland (Finland), the Sigrid Jusélius Foundation (Finland), the Emil Aaltonen Foundation (Finland), the University of Oulu Graduate School (Finland), the Norwegian Research Council (SYNKNØYT program), the General Medical Research Fund (University of Bergen, Norway), and Western Norway Regional Health Authority (Norway). We thank Dr. Marte Innselset Flydal for practical guidance in using DSC. We gratefully acknowledge the synchrotron radiation facilities and the beamline support at ANKA, ASTRID2, and EMBL/DESY, as well as the Partnership for Soft Condensed Matter facilities and neutron beamtimes at ILL (Proposal Nos 8-02-745 and 8-03-865). We also express our gratitude towards the Biocenter Oulu Proteomics and Protein Analysis Core Facility for providing access to mass spectrometric instrumentation.
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