Implications of the sequence similarities between tau and myelin basic protein.
The minor myelin basic protein (MBP) isoforms with M(r) 21.5 and 17 kDa and the cytoskeletal proteins actin and tubulin are enriched in an interlamellar junctional specialization within central nervous system (CNS) myelin, the radial component (RC). To pursue the notion that there are specific interactions between these constituents, we searched for sequences in MBP that are homologous to sequences in the tubulin-binding protein tau. We found that the sequence motifs that are homologous to the phosphorylation and tubulin binding sites of tau (-RSP- and -KPGFG-) are also within the exon 2 and 6-encoded peptides of MBP. The -KPGFG- motif is unique to MBP when compared to other myelin proteins, and is highly conserved in the MBPs among vertebrate species. The physicochemical properties of the MBP and tau peptides that contain these sequences and their predicted secondary structures suggest that the peptides containing these motifs are hydrophilic and folded largely in turn and coil. This implies that the motifs are located at the protein surface where they would be accessible for interactions with other components of proteins or lipids. We propose that these putative phosphorylation and tubulin-binding sites in MBP may play functional roles in CNS myelin that are analogous to their roles in tau.
Karthigasan
J
J
Children's Hospital, Boston, MA 02115, USA.
Inouye
H
H
Kirschner
D A
DA
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002490:Central Nervous System / Q000737:chemistry / Q000648:ultrastructure; D005091:Exons; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry* / Q000378:metabolism; D009186:Myelin Sheath / Q000737:chemistry / Q000648:ultrastructure; D010766:Phosphorylation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014404:Tubulin / Q000378:metabolism; D014714:Vertebrates / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry*
D004676:Myelin Basic Protein; D014404:Tubulin; D016875:tau Proteins