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Curr Protein Pept Sci. 2009 Jun;10(3):196-215.

The classic basic protein of myelin--conserved structural motifs and the dynamic molecular barcode involved in membrane adhesion and protein-protein interactions.

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Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada. N1G 2W1.


The myelin basic protein (MBP) family comprises a variety of developmentally-regulated members arising from different transcription start sites, differential splicing, and post-translational modifications. The "classic" isoforms of MBP include the 18.5 kDa form, which predominates in adult human myelin and facilitates compaction of the mature myelin sheath in the central nervous system, thereby maintaining its structural integrity. In addition to membrane-association, the 18.5 kDa and all other classic isoforms are able to interact with a multitude of proteins, including Ca(2+)-calmodulin, actin, tubulin, and SH3-domain containing proteins, and thus may be signalling linkers during myelin development and remodelling. All proteins in this family are intrinsically disordered, creating a large effective surface to facilitate multiple protein associations, and are post-translationally modified to various degrees by methylation, phosphorylation, and deimination. We have used spectroscopic (fluorescence, CD, EPR, and NMR) approaches to study MBP's conformational adaptability. A highly-conserved central domain presents an amphipathic alpha-helix in association with a phospholipid membrane, and contains a threonyl residue that is phosphorylated by MAP-kinases. In multiple sclerosis, this segment represents a primary immunodominant epitope. This helical structure is adjacent to a proline-rich region that presents a classic SH3-ligand, comprises a second MAP-kinase phosphorylation site, and forms a polyproline type II helix. This domain of the protein is thus essential to proper positioning of a protein-interaction motif, with the local conformation and accessibility being modulated by MAP-kinases. In addition, the C-terminus of 18.5 kDa MBP has been identified by NMR spectroscopy as a Ca(2+)-calmodulin-binding site, and is of note for having a high density of post-translational modifications (protein kinase C phosphorylation, and deimination). For the most part, any classic protein isoform functions as an entropic spring that interacts in its entirety with membranes and cytoskeletal proteins, but the central and C-terminal motifs may represent molecular switches.

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