MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge, Cambridgeshire CB2 0QH, UK.
Microscopy (Oxf). 2022 Feb 18;71(Supplement_1):i66-i71. doi: 10.1093/jmicro/dfab023.
Many new structures of membrane proteins have been determined over the last decade, yet the nature of protein-lipid interplay has received scant attention. The postsynaptic membrane of the neuromuscular junction and Torpedo electrocytes has a regular architecture, opening an opportunity to illuminate how proteins and lipids act together in a native membrane setting. Cryo electron microscopy (Cryo-EM) images show that cholesterol segregates preferentially around the constituent ion channel, the nicotinic acetylcholine receptor, interacting with specific sites in both leaflets of the bilayer. In addition to maintaining the transmembrane α-helical architecture, cholesterol forms microdomains - bridges of rigid sterol groups that link one channel to the next. This article discusses the whole protein-lipid organization of the cholinergic postsynaptic membrane, its physiological implications and how the observed details relate to our current concept of the membrane structure. I suggest that cooperative interactions, facilitated by the regular protein-lipid arrangement, help to spread channel activation into regions distant from the sites of neurotransmitter release, thereby enhancing the postsynaptic response.
在过去的十年中，已经确定了许多新的膜蛋白结构，但蛋白质-脂类相互作用的性质却很少受到关注。神经肌肉接头和电鳐电器官的突触后膜具有规则的结构，为阐明蛋白质和脂类如何在天然膜环境中协同作用提供了机会。冷冻电子显微镜（Cryo-EM）图像显示，胆固醇优先围绕组成离子通道，即烟碱型乙酰胆碱受体进行分隔，与双层膜的两个叶中的特定部位相互作用。除了维持跨膜α-螺旋结构外，胆固醇还形成微区 - 刚性甾醇基团的桥，将一个通道连接到另一个通道。本文讨论了胆碱能突触后膜的整个蛋白质 - 脂类组织，其生理意义以及观察到的细节如何与我们当前的膜结构概念相关。我认为，通过规则的蛋白质 - 脂类排列促进的协作相互作用有助于将通道激活传播到远离神经递质释放部位的区域，从而增强突触后反应。
