Abstract
The 18.5 kDa isoform of myelin basic protein (MBP) is a major component of the myelin sheath in the central nervous system of higher vertebrates, and a member of a larger family of proteins with a multiplicity of forms and post-translational modifications (PTMs). The 18.5 kDa protein is the exemplar of the family, being most abundant in adult myelin, and thus the most-studied. It is peripherally membrane-associated, but has generally been investigated in isolated form. MBP is an 'intrinsically unstructured' protein with a high proportion (∼75%) of random coil, but postulated to have core elements of β-sheet and α-helix. We review here the properties of the MBP family, especially of the 18.5 kDa isoform, and discuss how its three-dimensional (3D) structure may be resolved by direct techniques available to us, viz., X-ray and electron crystallography, and solution and solid-state NMR spectrometry. In particular, we emphasise that creating an appropriate environment in which the protein can adopt a physiologically relevant fold is crucial to such endeavours. By solving the 3D structure of 18.5 kDa MBP and the effects of PTMs, we will attain a better understanding of myelin architecture, and of the molecular mechanisms that transpire in demyelinating diseases such as multiple sclerosis.
Original language | English (US) |
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Pages (from-to) | 503-542 |
Number of pages | 40 |
Journal | Micron |
Volume | 35 |
Issue number | 7 |
DOIs | |
State | Published - Oct 2004 |
Externally published | Yes |
Keywords
- 2D crystals
- Actin
- Calmodulin
- Citrulline
- Crystallisation
- Deimination
- Electron crystallography
- Electron microscopy
- Electron paramagnetic resonance (EPR)
- Ganglioside
- Golli
- His-tag
- Intrinsically unstructured protein
- Magic angle spinning (MAS)
ASJC Scopus subject areas
- Structural Biology
- General Materials Science
- General Physics and Astronomy
- Cell Biology