Myelin Basic Protein Undergoes
a Broader Range of
Modifications in Mammals than in Lower Vertebrates
- Publication date
- Publisher
Abstract
Myelin basic protein (MBP) is an important component
of the myelin
sheath surrounding neurons, and it is directly affected in demyelinating
diseases. MBP contains a relatively large number of post-translational
modifications (PTMs), which have been reported to play a role in multiple
sclerosis, while MBPs from lower vertebrates have been reported to
be incapable of inducing multiple sclerosis or allergic encephalitis.
This study reveals the extent of differences in PTM patterns for mammalian
and nonmammalian MBPs. This included intact mass and de novo sequence
analysis of approximately 85% of rattlesnake MBP, the first reptile
MBP to be characterized, and of bovine MBP. We identified 12 PTMs
at 11 sites in the five bovine MBP charge components, which include
both previously reported and novel modifications. The most notable
modification is an acetylation of lysine 121. Other modifications
found in bovine MBP include N-terminal acetylation in components C1,
C2, and C3; oxidation of methionine 19 in all five components; all
charge isomers having both a mono- and dimethylated (symmetric) arginine
at position 106; deimination in arginines 23 and 47 found only in
component C8b; deimination of arginine 96 and deamidation in glutamine
102 found in components C2, C3, C8a, and C8b; phosphorylation in threonine
97 restricted to charge components C2 and C3; deimination in arginine
161 only found in component C3; deamidation of glutamine 120 was only
observed in C3. All four deiminated arginines and one acetylated lysine
were first experimentally revealed in this study for bovine MBP. Mascot
database searching combined with de novo sequence analysis of rattlesnake
MBP provided more than 85% sequence coverage. A few PTMs were also
revealed in rattlesnake MBP: mono- and dimethylated Arg, protein N-terminal
acetylation, and deiminated Arg. Overall, snake MBP was found to undergo
less modification than bovine MBP on the basis of the mass heterogeneity
of the intact protein, the bottom-up structure analysis, and the limited
complexity of rattlesnake MBP chromatography. The combined data from
this study and information from previous studies extend the known
MBP PTMs, and PTMs unique to higher vertebrates are proposed