Myelin Basic Protein, A Saucy Molecule With High Responsiveness to the Environment or Just an Unusual Membrane Protein? - Molecules: Nucleation, Aggregation and Crystallization - page 178

time in 1969 after extraction from defatted brain powder with HCl at pH
below 3 (Oshiro, Eylar, 1970). The final procedure was based on treatment
with urea and use of ion-exchange chromatography (Deibler et al ., 1972,
1984). Purified MBP — now referred to as classic MBP — was shown to
be an unfolded, water-soluble, and lipid-free protein (LF-MBP). In the
first report on the properties of the acid-extracted MBP, the protein was
described as a very asymmetric and extended ellipsoidal molecule with an
axial ratio near 10:1 (Eylar, Thompson, 1969). MBP appeared to be very
resistant to denaturation, with no significant role for hydrophobic and
hydrogen bonding in maintaining its structure. Other studies on the struc-
ture of LF-MBP in aqueous solution were in agreement with a flexible coil
conformation of the protein (Krigbaumand, Hsu, 1975; Gow, Smith, 1989;
Smith, 1992). On these grounds, the protein extracted with HCl might be
assigned to the family of IUPs.
The question may arise now whether this image of MBP may be a rea-
sonable representation of a membrane-associated, but possibly extrinsic,
protein or, in general, of a protein in a functional form. In other words, one
is left with the question whether the unfolded state and the absence of any
detectable biological activity in water correspond to the native physiolog-
ical environment of MBP, or whether this state is a consequence of the
drastic conditions of the extraction procedure from the myelin membrane.
In fact, there is no doubt that MBP is a protein associated to myelin and
should be considered, as it is, a membrane protein.
MBP as a membrane protein:The discovery
of lipid-bound MBP
Several studies have shown that LF-MBP can interact with detergents,
lipids, and other molecules, thereby assuming a more ordered structure
(Anthony, Moscarello, 1971; Burns et al ., 1981; Smith, 1982, 1992; Beniac
et al ., 1997; Haas et al ., 1998; Facci et al ., 2000; Polverini et al ., 2003; Hu
et al ., 2004; Cristofolini et al ., 2005; Rispoli et al ., 2007; Haas et al ., 2007).
Binding of MBP to lipids is in accord with the view that lipid-protein
interactions are critical for the stability of the myelin sheath (Boggs et al .,