TY - JOUR
T1 - Myelin basic protein - Diverse conformational states of an intrinsically unstructured protein and its roles in myelin assembly and multiple sclerosis
AU - Harauz, George
AU - Ishiyama, Noboru
AU - Hill, Christopher M.D.
AU - Bates, Ian R.
AU - Libich, David S.
AU - Farès, Christophe
N1 - Funding Information:
The work in this laboratory has been supported over the years by operating and equipment grants to GH from the Natural Sciences and Engineering Research Council of Canada, the Multiple Sclerosis Society of Canada, the Canadian Institutes of Health Research, and the Canada Foundation for Innovation. Gratitude is also extended to many collaborators and supporters, past and present, in no particular order: Drs Thomas Tompkins (Lallemand, Inc., Montréal, QC); Mario Moscarello, Denise Wood, Fabrizio Mastronardi, and Joan Boggs (Hospital for Sick Children, Toronto, ON); Peter Ottensmeyer and Mitsu Ikura (Ontario Cancer Institute, Toronto, ON), Tschangiz Scheybani, Reiner Hegerl, and Wolfgang Baumeister (Max-Planck-Institut für Biochemie, Martinsried, Germany); Andreas Engel (Biozentrum, Basel, Switzerland); Nick Viner and Phillip Matharu (University of Bristol, UK); Anthony and Celia Campagnoni (University of California at Los Angeles, CA); Paolo Riccio (University of Potenza, Italy); Eugenia Polverini and Paolo Cavatorta (University of Parma, Italy); Jan Sedzik (Karolinska Institutet, Sweden); Bing Jap (Lawrence Berkeley Laboratory, CA); Jimmy Feix (Medical College of Wisconsin, Milwaukee, WI); Terry Beveridge, Robert Harris, Vladimir Ladizhansky, and Valerie Robertson (University of Guelph, ON); Martine Monette and Henry Stronks (Bruker BioSpin Canada Ltd, Milton, ON).
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/10
Y1 - 2004/10
N2 - 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.
AB - 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.
KW - 2D crystals
KW - Actin
KW - Calmodulin
KW - Citrulline
KW - Crystallisation
KW - Deimination
KW - Electron crystallography
KW - Electron microscopy
KW - Electron paramagnetic resonance (EPR)
KW - Ganglioside
KW - Golli
KW - His-tag
KW - Intrinsically unstructured protein
KW - Magic angle spinning (MAS)
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UR - http://www.scopus.com/inward/citedby.url?scp=3042553626&partnerID=8YFLogxK
U2 - 10.1016/j.micron.2004.04.005
DO - 10.1016/j.micron.2004.04.005
M3 - Review article
C2 - 15219899
AN - SCOPUS:3042553626
SN - 0968-4328
VL - 35
SP - 503
EP - 542
JO - Zeitschrift fur wissenschaftliche Mikroskopie und mikroskopische Technik
JF - Zeitschrift fur wissenschaftliche Mikroskopie und mikroskopische Technik
IS - 7
ER -