Microstructural analysis of the effects of incorporation of myelin basic protein in phospholipid layers

Abstract

We report an X-ray reflectivity study on the effects of adsorption of myelin basic protein (MBP) on Langmuir monolayers and on deposited LangmuirSchaefer multilayers of the phospholipid dipalmitoyl phosphatidylglycerol (DPPG). We provide for the first time, direct microscopic evidence on the destructuring effects of MBP leading to plasticity of the DPPG layers supporting commonly accepted models of the stabilizing role of MBP in the myelin membrane. We also show how protein adsorption onto the layer is determined both by electrostatic and nonspecific hydrophobic interactions.

Assessment of Citrullinated Myelin by1H-MR Spectroscopy in Early-Onset Multiple Sclerosis

“…Thus, the interaction of MBP with lipids and its "glue activity" for adjacent bilayers are reduced. 11,12 In addition to such structural alterations, citrullinyl residues are associated with faster digestion of MBP by proteases. 4 The enzymes involved in deimination, peptidylarginine deiminases (PADs), have been found upregulated in MS due to hypomethylation of their promoter region.…”

The Role of Citrullinated Proteins Suggests a Novel Mechanism in the Pathogenesis of Multiple Sclerosis

“…MBP is postulated to work as a glue for adjacent bilayers [19, 20] by binding to the polar head groups. This mechanism of interaction is interfered with by deimination of arginyl residues, since the resulting citrulline carries a neutral charge.…”

A Thermodynamic and Structural Study of Myelin Basic Protein in Lipid Membrane Models

“…This effect is larger for anionic lipid films and it decreases as the film surface pressure increases (6). These results indicate that MBP strongly interacts with lipids; this interaction likely induces a conformational change of the protein molecule and makes MBP act as a surfactant (6,16,19,20,36). MBP can increase the surface pressure only when it is included, at least partially, into the monomolecular lipid film.…”

“…Cristofolini et al (20) recently reported that MBP, when added into the subphase of a DPPG Langmuir film, drastically increases the film roughness and suppresses its reflectivity at a surface pressure as high as 35 mN/m. We observed a similar effect in the DPPC film only at relatively low surface pressure (;10 mN/m), in agreement with the fact that at low surface pressures MBP penetrates the lipid layer, destroying its order.…”

“…Haas et al, from x-ray and neutron reflectivity measurements on LB films of dimyristoyl-La-phosphatidic acid (DMPA) and MBP, concluded that MBP forms a 1-nm-thick layer between the phospholipid polar heads (19). Cristofolini et al, using x-ray reflectivity measurements, found that MBP destroys the structural regularity of dipalmitoylphosphatidylglycerol (DPPG) monolayers at the air water/interface (20). Bates et al studied the interaction of recombinant murine MBP isomers with large unilamellar vesicles of physiological composition by electron paramagnetic resonance and showed that the N-terminal and C-terminal sites in the normal MBP are located below the plane of the phospholipid headgroups, whereas in the less cationic form that predominates in multiple sclerosis the C-terminal domain dissociates from the membrane (9).…”