Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom.
Biochemistry. 2010 Apr 27;49(16):3456-63. doi: 10.1021/bi100128h.
Saltatory conduction of nerve impulses along axonal membranes depends on the presence of a multilayered membrane, myelin, that wraps around the axon. Myelin basic protein (MBP) and myelin protein 2 (P2) are intimately involved in the generation of the myelin sheath. They are also implicated in a number of neurological diseases, including autoimmune diseases of both the central and peripheral nervous systems. Here, we have used atomic force microsopy (AFM) to study the effects of MBP and P2 on lipid bilayers. MBP in association with a mica substrate appeared unstructured, and tended to coat the mica surface in the form of a monolayer. In contrast, P2 appeared as discrete particles, with molecular volumes consistent with the formation of both monomers and dimers. Either MBP or P2, at micromolar concentrations, caused stacking of brain lipid bilayers. This stacking effect was significantly potentiated when both proteins were added together. Bilayers composed of phosphatidylcholine (PC) and phosphatidylserine (PS) were stacked by MBP, provided that cholesterol was also present; in contrast, P2 did not stack PC/PS/cholesterol bilayers. Hence, the bilayer stacking effects of the two proteins have different lipid requirements.
神经冲动沿着轴突膜的跳跃传导依赖于存在一个多层膜，髓鞘，它包裹在轴突周围。髓鞘碱性蛋白 (MBP) 和髓鞘蛋白 2 (P2) 密切参与髓鞘的生成。它们还与许多神经系统疾病有关，包括中枢和周围神经系统的自身免疫性疾病。在这里，我们使用原子力显微镜 (AFM) 研究了 MBP 和 P2 对脂质双层的影响。与云母基底结合的 MBP 表现出无结构，并且倾向于以单层的形式覆盖云母表面。相比之下，P2 呈现离散的颗粒状，分子体积与单体和二聚体的形成一致。以微摩尔浓度存在的 MBP 或 P2 都会导致脑脂质双层的堆积。当两种蛋白质一起添加时，这种堆积效应显著增强。由卵磷脂 (PC) 和磷脂酰丝氨酸 (PS) 组成的双层被 MBP 堆积，如果胆固醇也存在的话；相比之下，P2 不会堆积 PC/PS/胆固醇双层。因此，两种蛋白质的双层堆积效应有不同的脂质要求。
