Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory and University of California, Berkeley, California 94720, USA; email:
Annu Rev Biophys. 2019 May 6;48:45-61. doi: 10.1146/annurev-biophys-070317-032828. Epub 2019 Feb 20.
Impressive though the achievements of single-particle cryo-electron microscopy are today, a substantial gap still remains between what is currently accomplished and what is theoretically possible. As is reviewed here, twofold or more improvements are possible as regards () the detective quantum efficiency of cameras at high resolution, () converting phase modulations to intensity modulations in the image, and () recovering the full amount of high-resolution signal in the presence of beam-induced motion of the specimen. In addition, potential for improvement is reviewed for other topics such as optimal choice of electron energy, use of aberration correctors, and quantum metrology. With the help of such improvements, it does not seem to be too much to imagine that determining the structural basis for every aspect of catalytic control, signaling, and regulation, in any type of cell of interest, could easily be accelerated fivefold or more.
尽管单颗粒冷冻电子显微镜的成就令人印象深刻，但目前的实际成果与理论上的可能性之间仍存在着相当大的差距。正如这里所回顾的，在以下几个方面都有可能实现两倍甚至更多的改进：（）提高高分辨率相机的量子探测效率，（）将相位调制转换为图像中的强度调制，以及（）在样品受束流诱导运动的情况下恢复全部高分辨率信号。此外，还对其他主题进行了改进潜力的回顾，例如电子能量的最佳选择、像差校正器的使用以及量子计量学。借助这些改进，想象一下确定任何感兴趣类型的细胞中催化控制、信号传递和调节的各个方面的结构基础，能够轻松地加速五倍或更多倍，似乎也并非过分。
