Molecular structure and function of myelin protein P0 in membrane stacking
|Author:||Raasakka, Arne1,2; Ruskamo, Salla2; Kowal, Julia3,4;|
1Department of Biomedicine, University of Bergen, Bergen, Norway
2Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland
3Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum, University of Basel, Basel, Switzerland
4Institute of Molecular Biology and Biophysics, Department of Biology, ETH Zurich, Switzerland
5Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
6Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy
7Department of Sciences, University of Basilicata, Potenza, Italy
8Institute of Biological Interfaces (IBG-2), Karlsruhe Institute of Technology, Karlsruhe, Germany
9Institute of Organic Chemistry, Karlsruhe Institute of Technology, Karlsruhe, Germany
|Online Access:||PDF Full Text (PDF, 6.5 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe202003259175
|Publish Date:|| 2020-03-25
Compact myelin forms the basis of nerve insulation essential for higher vertebrates. Dozens of myelin membrane bilayers undergo tight stacking, and in the peripheral nervous system, this is partially enabled by myelin protein zero (P0). Consisting of an immunoglobulin (Ig)-like extracellular domain, a single transmembrane helix, and a cytoplasmic extension (P0ct), P0 harbours an important task in ensuring the integrity of compact myelin in the extracellular compartment, referred to as the intraperiod line. Several disease mutations resulting in peripheral neuropathies have been identified for P0, reflecting its physiological importance, but the arrangement of P0 within the myelin ultrastructure remains obscure. We performed a biophysical characterization of recombinant P0ct. P0ct contributes to the binding affinity between apposed cytoplasmic myelin membrane leaflets, which not only results in changes of the bilayer properties, but also potentially involves the arrangement of the Ig-like domains in a manner that stabilizes the intraperiod line. Transmission electron cryomicroscopy of native full-length P0 showed that P0 stacks lipid membranes by forming antiparallel dimers between the extracellular Ig-like domains. The zipper-like arrangement of the P0 extracellular domains between two membranes explains the double structure of the myelin intraperiod line. Our results contribute to the understanding of PNS myelin, the role of P0 therein, and the underlying molecular foundation of compact myelin stability in health and disease.
|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), and Western Norway Regional Health Authority (Norway).
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