Bioinformatics of Myelin Membrane Proteins - Molecules: Nucleation, Aggregation and Crystallization - page 44

carrying an N-linked glycan (consistent with an extracellular location),
while Ser residues in the region 226-243 are annotated as phosphorylated
(consistent with a cytosolic localization). The topology of the mature
protein (after removal of the signal peptide) is thus N out -1TM-C in , i.e. the
C-terminus is in the cytosol, cf. D'Urso et al ., (1990).

PMP22 protein

Human PMP22 (Uniprot Q01453) is 160 residues long. Like PLP1, it has
four clear hydrophobic regions that are all predicted to form transmem-
brane -helices (Fig. 4). Residue 41 is annotated in Uniprot as carrying

an N-linked glycan (consistent with an extracellular location) and both the
N- and C-termini have been localized to the cytosolic side of the mem-
brane by antibody mapping (D'Urso, 1997). Despite the high hydropho-
bicity of putative TM2 and TM3, antibody mapping of a construct with an
HA-tag inserted between residues 93 and 94 has localized this short loop
to the extracellular side of the membrane (Taylor, 2000), suggesting that
PMP22 may only have two bonafide TM

α

-helices (corresponding to the
most N- and C-terminal hydrophobic segments) and an N in -C in orientation.
Considering the rather high hydrophobicity of the second and third
hydrophobic segments, this is a rather surprising result that warrants
further study. The most peculiar nature of this protein is its lack of stain-
ability on SDS-PAGE by the silver method, and measured by circular
dichroism large content of

α

β -secondary structure in the presence of SDS

( Sedzik et al ., 2001).

PLP protein

Human PLP1 (Uniprot P60201) is 272 residues long. It has four clear
hydrophobic regions that are all predicted to form transmembrane
α -helices (Fig. 5). Antibody mapping studies have located the C-terminus

and a region around residues 103-116 to the cytosolic side of the plasma