Department of Biomedicine, University of Bergen, Bergen, Norway.
Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu, Finland.
Sci Rep. 2017 Jul 10;7(1):4974. doi: 10.1038/s41598-017-05364-3.
Compact myelin comprises most of the dry weight of myelin, and its insulative nature is the basis for saltatory conduction of nerve impulses. The major dense line (MDL) is a 3-nm compartment between two cytoplasmic leaflets of stacked myelin membranes, mostly occupied by a myelin basic protein (MBP) phase. MBP is an abundant myelin protein involved in demyelinating diseases, such as multiple sclerosis. The association of MBP with lipid membranes has been studied for decades, but the MBP-driven formation of the MDL remains elusive at the biomolecular level. We employed complementary biophysical methods, including atomic force microscopy, cryo-electron microscopy, and neutron scattering, to investigate the formation of membrane stacks all the way from MBP binding onto a single membrane leaflet to the organisation of a stable MDL. Our results support the formation of an amorphous protein phase of MBP between two membrane bilayers and provide a molecular model for MDL formation during myelination, which is of importance when understanding myelin assembly and demyelinating conditions.
紧凑髓鞘占髓鞘干重的大部分，其绝缘性质是神经冲动跳跃传导的基础。主要致密线（MDL）是堆叠的髓鞘膜的两个细胞质小叶片之间的 3nm 隔室，主要由髓鞘碱性蛋白（MBP）相占据。MBP 是一种丰富的髓鞘蛋白，与脱髓鞘疾病有关，如多发性硬化症。几十年来，人们一直在研究 MBP 与脂质膜的关联，但在生物分子水平上，MBP 驱动的 MDL 形成仍然难以捉摸。我们采用了互补的生物物理方法，包括原子力显微镜、冷冻电子显微镜和中子散射，来研究从 MBP 结合到单个膜小叶到稳定 MDL 组织的膜堆叠的形成。我们的结果支持 MBP 在两个膜双层之间形成无定形蛋白相，并为髓鞘形成过程中的 MDL 形成提供了分子模型，这对于理解髓鞘组装和脱髓鞘条件非常重要。
