Membrane-anchoring and charge effects in the interaction of myelin basic protein with lipid bilayers studied by site-directed spin labeling. J Biol Chem 2003 Aug 01;278(31):29041-7
Date
05/16/2003Pubmed ID
12748174DOI
10.1074/jbc.M302766200Scopus ID
2-s2.0-0041530267 (requires institutional sign-in at Scopus site) 74 CitationsAbstract
Myelin basic protein (MBP) maintains the compaction of the myelin sheath in the central nervous system by anchoring the cytoplasmic face of the two apposing bilayers and may also play a role in signal transduction. Site-directed spin labeling was done at eight matching sites in each of two recombinant murine MBPs, qC1 (charge +19) and qC8 charge (+13), which, respectively, emulate the native form of the protein (C1) and a post-translationally modified form (C8) that is increased in multiple sclerosis. When interacting with large unilamellar vesicles, most spin-labeled sites in qC8 were more mobile than those in qC1. Depth measurement via continuous wave power saturation indicated that the N-terminal and C-terminal sites in qC1 were located below the plane of the phospholipid headgroups. In qC8, the C-terminal domain dissociated from the membrane, suggesting a means by which the exposure of natural C8 to cytosolic enzymes and ligands might increase in vivo in multiple sclerosis. The importance of two Phe-Phe pairs in MBP to its interactions with lipids was investigated by separately mutating each pair to Ala-Ala. The mobility at F42A/F43A and especially F86A/F87A increased significantly. Depth measurements and helical wheel analysis indicated that the Phe-86/Phe-87 region could form a surface-seeking amphipathic alpha-helix.
Author List
Bates IR, Boggs JM, Feix JB, Harauz GAuthor
Jimmy B. Feix PhD Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Cell Membrane
Electron Spin Resonance Spectroscopy
Lipid Bilayers
Mice
Molecular Sequence Data
Multiple Sclerosis
Mutagenesis, Site-Directed
Myelin Basic Protein
Peptide Fragments
Protein Isoforms
Protein Structure, Secondary
Recombinant Proteins
Spin Labels
Static Electricity
Structure-Activity Relationship