-
Je něco špatně v tomto záznamu ?
Human myelin proteolipid protein structure and lipid bilayer stacking
S. Ruskamo, A. Raasakka, JS. Pedersen, A. Martel, K. Škubník, T. Darwish, L. Porcar, P. Kursula
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
275225
Biotieteiden ja Ympäristön Tutkimuksen Toimikunta
- MeSH
- axony metabolismus MeSH
- centrální nervový systém metabolismus MeSH
- lidé MeSH
- lipidové dvojvrstvy * metabolismus MeSH
- myelinová pochva metabolismus MeSH
- myelinový proteolipidový protein * metabolismus MeSH
- protein - isoformy metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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.
Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Biomedicine University of Bergen Bergen Norway
Department of Chemistry and Interdisciplinary Nanoscience Center Aarhus University Aarhus Denmark
Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu University of Oulu Oulu Finland
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc22025235
- 003
- CZ-PrNML
- 005
- 20221031100543.0
- 007
- ta
- 008
- 221017s2022 sz f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1007/s00018-022-04428-6 $2 doi
- 035 __
- $a (PubMed)35829923
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a sz
- 100 1_
- $a Ruskamo, Salla $u Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland. salla.ruskamo@oulu.fi $1 https://orcid.org/http://orcid.org/0000000297409077
- 245 10
- $a Human myelin proteolipid protein structure and lipid bilayer stacking / $c S. Ruskamo, A. Raasakka, JS. Pedersen, A. Martel, K. Škubník, T. Darwish, L. Porcar, P. Kursula
- 520 9_
- $a 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.
- 650 _2
- $a axony $x metabolismus $7 D001369
- 650 _2
- $a centrální nervový systém $x metabolismus $7 D002490
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a lipidové dvojvrstvy $x metabolismus $7 D008051
- 650 12
- $a myelinový proteolipidový protein $x metabolismus $7 D018991
- 650 _2
- $a myelinová pochva $x metabolismus $7 D009186
- 650 _2
- $a protein - isoformy $x metabolismus $7 D020033
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Raasakka, Arne $u Department of Biomedicine, University of Bergen, Bergen, Norway $1 https://orcid.org/http://orcid.org/0000000294439959
- 700 1_
- $a Pedersen, Jan Skov $u Department of Chemistry and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark
- 700 1_
- $a Martel, Anne $u Institut Laue-Langevin (ILL), Grenoble, France
- 700 1_
- $a Škubník, Karel $u Central European Institute of Technology, Masaryk University, Brno, Czech Republic
- 700 1_
- $a Darwish, Tamim $u National Deuteration Facility, The Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, Sydney, NSW, 2232, Australia
- 700 1_
- $a Porcar, Lionel $u Institut Laue-Langevin (ILL), Grenoble, France
- 700 1_
- $a Kursula, Petri $u Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland. petri.kursula@uib.no $u Department of Biomedicine, University of Bergen, Bergen, Norway. petri.kursula@uib.no $1 https://orcid.org/http://orcid.org/0000000185293751
- 773 0_
- $w MED00001078 $t Cellular and molecular life sciences $x 1420-9071 $g Roč. 79, č. 8 (2022), s. 419
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/35829923 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20221017 $b ABA008
- 991 __
- $a 20221031100541 $b ABA008
- 999 __
- $a ok $b bmc $g 1854772 $s 1176525
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2022 $b 79 $c 8 $d 419 $e 20220712 $i 1420-9071 $m Cellular and molecular life sciences $n Cell Mol Life Sci $x MED00001078
- GRA __
- $a 275225 $p Biotieteiden ja Ympäristön Tutkimuksen Toimikunta
- LZP __
- $a Pubmed-20221017
