MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Faraday Discuss. 2022 Nov 8;240(0):277-302. doi: 10.1039/d2fd00076h.
Electron cryomicroscopy (cryoEM) has made great strides in the last decade, such that the atomic structure of most biological macromolecules can, at least in principle, be determined. Major technological advances - in electron imaging hardware, data analysis software, and cryogenic specimen preparation technology - continue at pace and contribute to the exponential growth in the number of atomic structures determined by cryoEM. It is now conceivable that within the next decade we will have structures for hundreds of thousands of unique protein and nucleic acid molecular complexes. But the answers to many important questions in biology would become obvious if we could identify these structures precisely inside cells with quantifiable error. In the context of an abundance of known structures, it is appropriate to consider the current state of electron cryomicroscopy for frozen specimens prepared directly from cells, and try to answer to the question of the title, both now and in the foreseeable future.
电子冷冻显微镜(cryoEM)在过去十年中取得了重大进展,以至于大多数生物大分子的原子结构至少在理论上都可以确定。主要技术进步——电子成像硬件、数据分析软件和低温标本制备技术——正在加速发展,并促进了通过 cryoEM 确定的原子结构数量的指数增长。现在可以想象,在未来十年内,我们将拥有数十万种独特的蛋白质和核酸分子复合物的结构。但是,如果我们能够以可量化的误差在细胞内精确地识别这些结构,那么许多生物学中的重要问题的答案将变得显而易见。在大量已知结构的背景下,适当地考虑当前直接从细胞中制备的冷冻标本的电子冷冻显微镜的状态,并尝试回答这个问题,无论是现在还是可预见的未来。