Human myelin proteolipid protein structure and lipid bilayer stacking
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F22%3A00128474" target="_blank" >RIV/00216224:14740/22:00128474 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s00018-022-04428-6" target="_blank" >https://link.springer.com/article/10.1007/s00018-022-04428-6</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00018-022-04428-6" target="_blank" >10.1007/s00018-022-04428-6</a>
Alternative languages
Result language
angličtina
Original language name
Human myelin proteolipid protein structure and lipid bilayer stacking
Original language description
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, alpha-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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LM2018127" target="_blank" >LM2018127: Czech Infrastructure for Integrative Structural Biology</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cellular and molecular life sciences
ISSN
1420-682X
e-ISSN
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Volume of the periodical
79
Issue of the periodical within the volume
8
Country of publishing house
CH - SWITZERLAND
Number of pages
19
Pages from-to
419
UT code for WoS article
000824644400001
EID of the result in the Scopus database
2-s2.0-85134252456