Bioinformatics of Myelin Membrane Proteins - Molecules: Nucleation, Aggregation and Crystallization - page 50

the hydrophobic nature of the second hydrophobic domain, the presence
of two proline residues near the middle of the hydrophobic stretch, and
positively charged residues on both flanks, it is possible that this segment
forms a short “helical hairpin” that penetrates only partly across the mem-
brane (Monné et al ., 1999; Sääf et al ., 2000). The segment is protected
from protease attack and cannot be extracted from membranes with
chaotropic agents (della Gaspera, 1998). So far, MOG is the only candi-
date autoantigen responsible for causing multiple sclerosis (Bernard et al .,
1997).

Summary

Explaining how the myelin proteins are involved in the organization and
function of the myelin sheath requires knowing their molecular structures.
From the bioinformatics analysis presented above, along with published
experimental data, we conclude that MBP and P2 are both cytosolic and
either soluble or peripherally bound to the myelin membrane. P0 and
MAG both have a cleavable signal peptide and a C-terminal transmem-
brane anchor. The same conclusion was made by Kirschner and Inouye
(1991): their comparison of the corresponding myelin basic proteins
(MBP) and P0 glycoproteins for rodent and shark showed that the con-
served residues included most of the amino acids which were predicted to
form the alpha or beta conformations, while the altered residues were
mainly in the hydrophilic and turn or coil regions. In both rodent and
shark the putative extracellular domain of P0 glycoprotein displayed con-
secutive peaks of beta propensity similar to that for the immunoglobulins,
while the cytoplasmic domain showed alpha-beta-alpha folding. The
flat -sheets of P0 are orientated parallel to the membrane surface to facil-

itate their homotypic interaction in the extracellular space (Inouye,
Kirschner, 1991).
PLP has four transmembrane helices, and PMP22 has either two or four
transmembrane helices, and both proteins have their N- and C-termini
orientated towards the cytosol. MOG, finally, has a signal peptide and one
transmembrane helix. A second, markedly hydrophobic segment in the

β