Abstract
Myelin basic protein (MBP) is located in the insulating covers of nerve cells in the brain and spinal cord. By interacting with lipid membranes, it is responsible for compaction of the myelin sheath in the central nervous system, which is weakened in demyelinating diseases. The lipid composition of the myelin leaflet has a high impact on the interaction between the membrane and MBP. Cholesterol is present in the cytoplasmic leaflet with a rather high amount of 44% (mol%). In this study, the focus is on the effect of cholesterol, mainly by varying its content, on the interaction of MBP with a lipid monolayer. Therefore, Langmuir lipid monolayers mimicking the cytoplasmic membrane of myelin and monolayers with variations of cholesterol content between 0% and 100% were measured at the air/water interface with additional imaging by fluorescence microscopy. All experiments were performed with and without bovine MBP to study the dependence of the interaction of the protein with the monolayers on the cholesterol content. The native amount of 44% cholesterol in the monolayer combines optima in the order of the monolayer (presumably correlating to compaction and thermodynamic stability) and protein interaction and shows unique features in comparison to lower or higher cholesterol contents.
Highlights
Myelin basic protein (MBP) may play a decisive role in the elucidation of multiple sclerosis, for the early stages in progression of this highly debilitating, demyelinating autoimmune disease
post-translational modifications (PTMs) and mutations in myelin proteins lead to neuropathies such as multiple sclerosis, which manifests itself in progressive demyelination [1]
If we compare the experimental results of lipid monolayers with 10% and 44% cholesterol, we find that in the former MBP incorporates itself “more favorably” into the monolayer, meaning that high surface pressures are reached at larger surface areas (Figure 2, black and magenta), and the protein interacts more favorably with the lipid monolayer
Summary
Myelin basic protein (MBP) may play a decisive role in the elucidation of multiple sclerosis, for the early stages in progression of this highly debilitating, demyelinating autoimmune disease. There are charge variants of MBP, usually termed along decreasing net positive charge from. PTMs and mutations in myelin proteins lead to neuropathies such as multiple sclerosis, which manifests itself in progressive demyelination [1]. The mainly unmodified C1 variant has a net charge of. In severe cases of MS and in animal models such as EAE (experimental autoimmune encephalomyelitis), the modified, charge-reduced variants, in particular down to C8. (net charge of +13 at pH 7) are found in much greater abundance [3,4].
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