Myelin basic protein-diverse conformational states of an intrinsically unstructured protein and its roles in myelin assembly and multiple sclerosis.
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 (approximately 75%) of random coil, but postulated to have core elements of beta-sheet and alpha-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.
Harauz
George
G
Department of Molecular Biology and Genetics, Biophysics Interdepartmental Group, University of Guelph, Room 230, Axelrod Building, 50 Stone Road East, Guelph, Ont., Canada N1G 2W1. gharauz@uoguelph.ca
Ishiyama
Noboru
N
Hill
Christopher M D
CM
Bates
Ian R
IR
Libich
David S
DS
Farès
Christophe
C
D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000737:chemistry* / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D004676:Myelin Basic Protein