University of Oulu

Ruskamo, S., Raasakka, A., Pedersen, J.S. et al. Human myelin proteolipid protein structure and lipid bilayer stacking. Cell. Mol. Life Sci. 79, 419 (2022).

Human myelin proteolipid protein structure and lipid bilayer stacking

Saved in:
Author: Ruskamo, Salla1; Raasakka, Arne2; Pedersen, Jan Skov3;
Organizations: 1Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland
2Department of Biomedicine, University of Bergen, Bergen, Norway
3Department of Chemistry and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark
4Institut Laue-Langevin (ILL), Grenoble, France
5Central European Institute of Technology, Masaryk University, Brno, Czech Republic
6National Deuteration Facility, The Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, Sydney, NSW, 2232, Australia
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.8 MB)
Persistent link:
Language: English
Published: Springer Nature, 2022
Publish Date: 2022-12-27


The myelin sheath is an essential, multilayered membrane structure that insulates axons, enabling the rapid transmission of nerve impulses. The tetraspan myelin proteolipid protein (PLP) is the most abundant protein of compact myelin in the central nervous system (CNS). The integral membrane protein PLP adheres myelin membranes together and enhances the compaction of myelin, having a fundamental role in myelin stability and axonal support. PLP is linked to severe CNS neuropathies, including inherited Pelizaeus-Merzbacher disease and spastic paraplegia type 2, as well as multiple sclerosis. Nevertheless, the structure, lipid interaction properties, and membrane organization mechanisms of PLP have remained unidentified. We expressed, purified, and structurally characterized human PLP and its shorter isoform DM20. Synchrotron radiation circular dichroism spectroscopy and small-angle X-ray and neutron scattering revealed a dimeric, α-helical conformation for both PLP and DM20 in detergent complexes, and pinpoint structural variations between the isoforms and their influence on protein function. In phosphatidylcholine membranes, reconstituted PLP and DM20 spontaneously induced formation of multilamellar myelin-like membrane assemblies. Cholesterol and sphingomyelin enhanced the membrane organization but were not crucial for membrane stacking. Electron cryomicroscopy, atomic force microscopy, and X-ray diffraction experiments for membrane-embedded PLP/DM20 illustrated effective membrane stacking and ordered organization of membrane assemblies with a repeat distance in line with CNS myelin. Our results shed light on the 3D structure of myelin PLP and DM20, their structure–function differences, as well as fundamental protein–lipid interplay in CNS compact myelin.

see all

Series: Cellular and molecular life sciences
ISSN: 1420-682X
ISSN-E: 1420-9071
ISSN-L: 1420-682X
Volume: 79
Issue: 8
Article number: 419
DOI: 10.1007/s00018-022-04428-6
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: Open Access funding provided by University of Oulu including Oulu University Hospital. This work was funded by the Academy of Finland, grant number 275225 and Jane and Aatos Erkko Foundation. Beamtime and user support at EMBL/DESY, SOLEIL, ILL and ISA are gratefully acknowledged. Travel to synchrotrons was supported by the European Union Horizon 2020 programs iNEXT (Grant 653706) and CALIPSOplus (Grant 730872). The National Deuteration Facility at ANSTO is partly funded by The National Collaborative Research Infrastructure Strategy (NCRIS), an Australian Government initiative. We acknowledge the cryo-electron microscopy and tomography core facility CEITEC MU of CIISB, Instruct-CZ Centre supported by MEYS CR (LM2018127).
EU Grant Number: (653706) iNEXT - Infrastructure for NMR, EM and X-rays for translational research
Academy of Finland Grant Number: 275225
Detailed Information: 275225 (Academy of Finland Funding decision)
Dataset Reference: The small-angle X-ray scattering and diffraction datasets generated during the current study are available in the Zenodo repository, using and the small-angle neutron scattering dataset in the ILL neutron data repository, using
Copyright information: © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit