Titre
Molecular structure and function of myelin protein P0 in membrane stacking.
Type
article
Institution
Externe
Périodique
Auteur(s)
Raasakka, A.
Auteure/Auteur
Ruskamo, S.
Auteure/Auteur
Kowal, J.
Auteure/Auteur
Han, H.
Auteure/Auteur
Baumann, A.
Auteure/Auteur
Myllykoski, M.
Auteure/Auteur
Fasano, A.
Auteure/Auteur
Rossano, R.
Auteure/Auteur
Riccio, P.
Auteure/Auteur
Bürck, J.
Auteure/Auteur
Ulrich, A.S.
Auteure/Auteur
Stahlberg, H.
Auteure/Auteur
Kursula, P.
Auteure/Auteur
Liens vers les personnes
ISSN
2045-2322
Statut éditorial
Publié
Date de publication
2019-01-24
Volume
9
Numéro
1
Première page
642
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
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.
PID Serval
serval:BIB_2DC7E8BEC46D
PMID
Open Access
Oui
Date de création
2023-06-09T14:02:24.623Z
Date de création dans IRIS
2025-05-20T19:12:23Z