The effect of basic myelin protein on multilayer membrane formation

Abstract

The myelin membrane is composed of 75-80% lipids and 20-25% proteins. The lipids are organized into regular multilayers, with the protein incorporated in them. The protein fraction has been found to be relatively simple in comparison with that of plasma membranes, in that two types of protein make up 70-85% of the total membrane protein (Boggs and Moscarello, 1978a). The first of these, the basic protein, makes up about 35% of the total protein, whereas the second, the proteolipid, makes up about 50%. The proteolipid consists mainly of lipophilin with lesser amounts of Wolfgram proteins, some glycoprotein, and a few enzymes.We have been engaged in a series of studies on the interaction of these two types of protein with phospholipid, using liquid x-ray diffraction techniques. The first of these, on the lipophilin (N-2)-phosphatidyl choline system (Brady et al., 1979a,b,c) showed that this protein was incorporated into the interior of the bilayer in highly associated form, and that as more protein was incorporated, the multilayer structure was broken down to give way to single bilayers. Because the myelin membrane in its native form is a highly organized multilayer structure, it is of interest to see how the incorporation of the hydrophilic basic protein affects the multilayer structure and whether it counterbalances the disrupting effect of the lipophilin. It is also important to determine whether the basic protein exists in extended form in the membranes or whether it too is associated. In this brief communication, we present results of some studies on the interaction of basic protein with phospholipid, using egg phosphatidyl glycerol (PG) as a prototype acidic lipid. PG was used because it is easily obtained and interacts well with basic protein to form stable liposomes. The interaction is similar to that of other acidic lipids, including nerve myelin (phosphatidyl serine, cerebroside sulphate) which has been extensively studied by DSC, ESR and NMR. The results shed light on the two questions raised above.Basic protein was purified from normal white matter (Lowden et al., 1966). Vesicles containing the protein were prepared according to Boggs and Moscarello (1978b). Egg PG was dissolved in 100% redistilled 2-chloroethanol, 5 mg/ml. Lyophilized myelin basic protein was dissolved in 100% redistilled 2-chloroethanol, 5 mg/ml. The lipid and protein solutions BIoPHYs.J.©BiophysicalSociety -0006-3495/

Characterization of a Recombinant Murine 18.5-kDa Myelin Basic Protein

“…2 is one of the principal constituents of the mammalian myelin sheath and plays a structural role in maintaining myelin stability (1)(2)(3)(4)(5)(6). Immune responses to MBP have been implicated in the pathogenesis of multiple sclerosis (MS), the most common autoimmune disease of the central nervous system in North America and Northern Europe (7,8).…”

Multilamellar packing of myelin modeled by lipid-bound MBP

“…Moreover, MBP develops some secondary structure upon binding to lipids or detergents. Also informative are the studies that localize MBP after insertion into lipid multilayers (Mateu et al, 1973;Demel et al, 1973;Verkleij et al, 1974;Smith, 1977Smith, , 1992Brady et al, 1981;Lampe et al, 1983;Sedzik et al, 1984;MacNaughtan et al, 1985;Haas et al, 1998). However, nearly all of these studies use the aqueous form of MBP, which in being separated from myelin lipids, has lost any substantial secondary structure.…”

“…Several studies have demonstrated that MBP, which is an extrinsic, water-soluble protein, can interact with specific lipids and detergents to form ordered assemblies (Smith, 1992) including monolayers (Demel et al, 1973;MacNaughtan et al, 1985) and stacks of bilayers (Mateu et al, 1973;Verkleij et al, 1974;Smith, 1977;Brady et al, 1981;Sedzik et al, 1984;MacNaughtan et al, 1985). Three different experimental approaches have been reported.…”

The Influence of the Myelin Basic Protein C8 Mutant on the Dynamics of Myelin Membranes

“…Myelin is electrically insulating the axons, allowing fast, saltatory nerve impulse conduction. The composition [3,4,5,6,7,8] and structure [9,10] of the myelin sheath are well studied. Myelin is a lipid-rich membrane, composed of 75 -80% anionic and neutral lipids and 20 -25% proteins [8].…”

“…The composition [3,4,5,6,7,8] and structure [9,10] of the myelin sheath are well studied. Myelin is a lipid-rich membrane, composed of 75 -80% anionic and neutral lipids and 20 -25% proteins [8]. A subset of myelin-specific proteins, which interact closely with the membrane, is well known [11], but little is known about their influence on the membrane structure and dynamics.…”