The classic isoforms of myelin basic protein (MBP, 14–21.5 kDa) are essential to formation of the multilamellar myelin sheath of the mammalian central nervous system (CNS). The predominant 18.5-kDa isoform links together the cytosolic surfaces of oligodendrocytes, but additionally participates in cytoskeletal turnover and membrane extension, Fyn-mediated signalling pathways, sequestration of phosphoinositides and maintenance of calcium homoeostasis. All MBP isoforms are intrinsically disordered proteins (IDPs) that interact via molecular recognition fragments (MoRFs), which thereby undergo local disorder-to-order transitions. Their conformations and associations are modulated by environment and by a dynamic barcode of post-translational modifications, particularly phosphorylation by mitogen-activated and other protein kinases and deimination [a hallmark of demyelination in multiple sclerosis (MS)]. The MBPs are thus to myelin what basic histones are to chromatin. Originally thought to be merely structural proteins forming an inert spool, histones are now known to be dynamic entities involved in epigenetic regulation and diseases such as cancer. Analogously, the MBPs are not mere adhesives of compact myelin, but active participants in oligodendrocyte proliferation and in membrane process extension and stabilization during myelinogenesis. A central segment of these proteins is pivotal in membrane-anchoring and SH3 domain (Src homology 3) interaction. We discuss in the present review advances in our understanding of conformational conversions of this classic basic protein upon membrane association, including new thermodynamic analyses of transitions into different structural ensembles and how a shift in the pattern of its post-translational modifications is associated with the pathogenesis and potentially onset of demyelination in MS.
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November 2015
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Review Article|
October 30 2015
MyelStones: the executive roles of myelin basic protein in myelin assembly and destabilization in multiple sclerosis
Kenrick A. Vassall;
Kenrick A. Vassall
*Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada, N1G 2W1
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Vladimir V. Bamm;
Vladimir V. Bamm
*Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada, N1G 2W1
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George Harauz
George Harauz
1
*Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada, N1G 2W1
1To whom correspondence should be addressed (email gharauz@uoguelph.ca).
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Publisher: Portland Press Ltd
Received:
July 03 2015
Revision Received:
August 28 2015
Accepted:
September 04 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2015 Authors; published by Portland Press Limited
2015
Biochem J (2015) 472 (1): 17–32.
Article history
Received:
July 03 2015
Revision Received:
August 28 2015
Accepted:
September 04 2015
Citation
Kenrick A. Vassall, Vladimir V. Bamm, George Harauz; MyelStones: the executive roles of myelin basic protein in myelin assembly and destabilization in multiple sclerosis. Biochem J 15 November 2015; 472 (1): 17–32. doi: https://doi.org/10.1042/BJ20150710
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