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Myelin basic protein (MBP) charge variants show different sphingomyelin-mediated interactions with myelin-like lipid monolayers.
Biochimica et Biophysica Acta (BBA) - Biomembranes ( IF 2.8 ) Pub Date : 2019-12-02 , DOI: 10.1016/j.bbamem.2019.183077
Katharina Widder 1 , George Harauz 2 , Dariush Hinderberger 1
Affiliation  

Multiple sclerosis (MS) is correlated with increased deimination of myelin basic protein (MBP) in the central nervous system. Here, the interaction of MBP C1 (charge: +19) and MBP C8 (charge: +13) with the major lipids of the cytoplasmic side of the oligodendrocyte membrane is analysed using monolayer adsorption experiments and epifluorescence microscopy. Our findings show that the electrostatic attraction between the positively charged proteins and negatively charged lipids in the myelin-like monolayers competes with the incorporation of MBP into regions directly bordering cholesterol-rich domains. The latter is favoured to avoid additional lipid condensation and reduction in fluidity of the phospholipid layer. We find that MBP C1 does not incorporate at the cholesterol-rich domains if sphingomyelin (SM) is absent from the lipid composition. In contrast, MBP C8 is still incorporated near cholesterol-enriched regions without SM. Thus, the highly charged C1 variant needs a specific interaction with SM, whereas for C8 the incorporation at the cholesterol-rich regions is ensured due to its reduced net positive charge. This phenomenon may be relevant for the correlation of higher amounts of MBP C8 in brains of adult MS patients and healthy children, in which the amount of SM is reduced compared to healthy adults.

中文翻译:

髓磷脂碱性蛋白(MBP)电荷变异体显示鞘磷脂介导的与髓磷脂样脂质单层的相互作用。

多发性硬化症(MS)与中枢神经系统中髓鞘碱性蛋白(MBP)的脱脂增加有关。在这里,使用单层吸附实验和落射荧光显微镜分析MBP C1(电荷:+19)和MBP C8(电荷:+13)与少突胶质细胞膜细胞质侧主要脂质的相互作用。我们的发现表明,髓磷脂样单层中带正电的蛋白质和带负电的脂质之间的静电吸引与MBP掺入直接与富含胆固醇的区域接壤的区域竞争。后者是有利的,以避免额外的脂质缩合和磷脂层的流动性降低。我们发现,如果脂质成分中不包含鞘磷脂(SM),则MBP C1不会在富含胆固醇的域中掺入。相反,MBP C8仍在没有SM的胆固醇丰富区域附近掺入。因此,高电荷的C1变体需要与SM进行特定的相互作用,而对于C8,由于其净正电荷减少,因此可以确保在胆固醇丰富的区域掺入。这种现象可能与成年MS患者和健康儿童大脑中MBP C8含量较高的相关性有关,与健康成年人相比,SMP的含量降低了。
更新日期:2019-12-03
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