hide
Free 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); MTS-SL (methanethiosulphonate-spin label); Multiple sclerosis; Myelin basic protein; Natively unfolded protein; Nuclear magnetic resonance (NMR); Phosphatidylinositol; Protein–lipid interactions; Recombinant proteins; Site-directed mutagenesis; Site-directed spin labelling (SDSL); Solid-state NMR; Solution NMR
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.
