Membrane proteins represent a large proportion of the proteome, but have characteristics that are problematic for many methods in modern molecular biology (that have often been developed with soluble proteins in mind). For structural studies, low levels of expression and the presence of detergent have been thorns in the flesh of the membrane protein experimentalist. Here we discuss the use of cryo-electron microscopy in breakthrough studies of the structures of membrane proteins. This method can cope with relatively small quantities of sample and with the presence of detergent. Until recently, cryo-electron microscopy could not deliver high-resolution structures of membrane proteins, but recent developments in transmission electron microscope technology and in the image processing of single particles imaged in the microscope have revolutionized the field, allowing high resolution structures to be obtained. Here we focus on the specific issues surrounding the application of cryo-electron microscopy to the study of membrane proteins, especially in the choice of a system to keep the protein soluble.

膜蛋白在蛋白质组中占很大比例，但是具有现代分子生物学中许多方法都存在问题的特征（通常在开发时就考虑了可溶性蛋白）。对于结构研究，低水平的表达和去污剂的存在已成为膜蛋白实验人员的骨肉。在这里，我们讨论了在膜蛋白结构突破研究中使用冷冻电子显微镜。该方法可以处理相对少量的样品并存在清洁剂。直到最近，低温电子显微镜还无法提供高分辨率的膜蛋白结构，但是，透射电子显微镜技术和显微镜中成像的单个颗粒的图像处理的最新发展彻底改变了该领域，从而获得了高分辨率的结构。在这里，我们将重点放在围绕低温电子显微镜技术应用于膜蛋白研究的具体问题上，尤其是在选择一种保持蛋白可溶的系统方面。