Myelin basic protein (MBP) charge variants show different sphingomyelin-mediated interactions with myelin-like lipid monolayers.
Myelin basic protein (MBP) charge variants show different sphingomyelin-mediated interactions with myelin-like lipid monolayers.
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髓磷脂碱性蛋白 (MBP) 电荷变体表现出不同的鞘磷脂介导的与髓磷脂样脂质单层的相互作用
DOI：
10.1016/j.bbamem.2019.183077
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Dariush Hinderberger
中科院分区：
文献类型：
--
作者：
Katharina Widder;George Harauz;Dariush Hinderberger
多发性硬化症（MS）与中枢神经系统中髓鞘碱性蛋白（MBP）脱亚胺化增加有关。在这里，MBP C1（电荷：+19）和MBP C8（电荷：+13）与少突胶质细胞膜的细胞质侧的主要脂质的相互作用进行了分析，使用单层吸附实验和落射荧光显微镜。我们的研究结果表明，带正电荷的蛋白质和带负电荷的脂质在髓鞘样单层之间的静电吸引力的竞争与MBP的纳入直接接壤的区域富含胆固醇的域。后者有利于避免额外的脂质凝结和磷脂层流动性的降低。我们发现，MBP C1不纳入在富含胆固醇的结构域，如果鞘磷脂（SM）是不存在的脂质组合物。相比之下，MBP C8仍然被纳入附近的胆固醇富集的区域没有SM。因此，高电荷的C1变体需要与SM特异性相互作用，而对于C8，由于其减少的净正电荷，确保了在富含胆固醇的区域的掺入。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，其中与健康成人相比，SM的含量减少。
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.
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影响因子：
4.8
作者：
Garcia-Saez, Ana J.;Chiantia, Salvatore;Schwille, Petra
通讯作者：
Schwille, Petra
影响因子：
--
作者：
MCCONNELL, HM;MOY, VT
通讯作者：
MOY, VT
影响因子：
3.5
作者：
FINCH, PR;WOOD, DD;MOSCARELLO, MA
通讯作者：
MOSCARELLO, MA
DOI：
10.1073/pnas.0405665101
发表时间：
2004-09-14
影响因子：
11.1
作者：
Hu, YF;Doudevski, I;Israelachvili, J
通讯作者：
Israelachvili, J
人类中枢神经系统髓磷脂 1 的生化成熟
影响因子：
4.7
作者：
M. Fishman;H. Agrawal;A. Alexander;J. Golterman;R. Martenson;R. F. Mitchell
通讯作者：
R. F. Mitchell