Myelin basic protein - Diverse conformational states of an intrinsically unstructured protein and its roles in myelin assembly and multiple sclerosis

George Harauz, Noboru Ishiyama, Christopher M.D. Hill, Ian R. Bates, David S. Libich, Christophe Farès

Research output: Contribution to journalReview articlepeer-review

195 Scopus citations

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 languageEnglish (US)
Pages (from-to)503-542
Number of pages40
JournalMicron
Volume35
Issue number7
DOIs
StatePublished - Oct 2004
Externally publishedYes

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
  • Materials Science(all)
  • Physics and Astronomy(all)
  • Cell Biology

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